Frameless Stereotactic Radiosurgery Research Articles

Clinicogenomic predictors of survival and intracranial progression after stereotactic radiosurgery for colorectal cancer brain metastases.

Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS). Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk. This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01). The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.

Frameless LINAC Stereotactic Radiosurgery for Brain Metastasis using VMAT: A Review of 20 Cases and Institutional Experience

Background/Objectives: Brain metastases can be treated with Stereotactic Radiosurgery (SRS), a precise radiation therapy approach. This study aimed to review the feasibility and efficacy of frameless LINAC-based SRS using Volumetric Modulated Arc Therapy (VMAT) in a group of 20 patients. Methods: Twenty patients diagnosed with brain metastases received VMAT SRS. Clinical characteristics such as demographics, gender, performance status, number of brain metastases, neurological symptoms, neurosurgical procedures, systemic status, prior treatments, lesion size, SRS dose, local control after SRS and toxicity profile were assessed. Results: The median age of patients was 49.5 years (range 32-63), with 80% being female. Most patients (85%) had ECOG scores of 0-1. The median lesion size treated was 16 mm, with a median dose of 20 Gy for the first SRS (SRS1). After SRS1, 75% of patients achieved Local Control (LC), with a median duration of LC of 7.65 months. Six patients received a second SRS (SRS2) with a median dose of 20 Gy to a different location. Two out of six patients achieved LC after SRS2. Radiation necrosis occurred in 2 cases (10%). The median follow-up time from brain metastasis to the last follow-up was 20.31 months (range 0-50.43 months). Conclusion: Frameless LINAC-based VMAT SRS appears to be a promising treatment option for brain metastases. Initial findings suggest favorable local control rates and further research is needed to optimize treatment strategies.

Frameless LINAC Stereotactic Radiosurgery for Brain Metastasis using VMAT: A Review of 20 Cases and Institutional Experience

Background/Objectives: Brain metastases can be treated with Stereotactic Radiosurgery (SRS), a precise radiation therapy approach. This study aimed to review the feasibility and efficacy of frameless LINAC-based SRS using Volumetric Modulated Arc Therapy (VMAT) in a group of 20 patients. Methods: Twenty patients diagnosed with brain metastases received VMAT SRS. Clinical characteristics such as demographics, gender, performance status, number of brain metastases, neurological symptoms, neurosurgical procedures, systemic status, prior treatments, lesion size, SRS dose, local control after SRS and toxicity profile were assessed. Results: The median age of patients was 49.5 years (range 32-63), with 80% being female. Most patients (85%) had ECOG scores of 0-1. The median lesion size treated was 16 mm, with a median dose of 20 Gy for the first SRS (SRS1). After SRS1, 75% of patients achieved Local Control (LC), with a median duration of LC of 7.65 months. Six patients received a second SRS (SRS2) with a median dose of 20 Gy to a different location. Two out of six patients achieved LC after SRS2. Radiation necrosis occurred in 2 cases (10%). The median follow-up time from brain metastasis to the last follow-up was 20.31 months (range 0-50.43 months). Conclusion: Frameless LINAC-based VMAT SRS appears to be a promising treatment option for brain metastases. Initial findings suggest favorable local control rates and further research is needed to optimize treatment strategies.

Frameless Linear Accelerator (LINAC) Based Radiosurgery (SRS) vs. Framed Gamma Knife SRS for Idiopathic Trigeminal Neuralgia (TN)

Stereotactic radiosurgery (SRS) is an effective treatment for idiopathic trigeminal neuralgia (TN). Conventional treatment is done through frame-based solution due to small target and high radiation dose. More recently, LINAC based frameless SRS technique has been established as a patient friendly alternative. Herein we compared our single institution experience of LINAC based frameless SRS vs frame-based gamma knife SRS for TN. The hypothesis is LINAC based frameless SRS can provide equivalent dosimetric and clinical outcome as compared frame-based gamma knife treatment. Patients with idiopathic TN who received SRS treatment (LINAC based frameless treatment or Gamma knife framed treatment) at our institution from 2015-2022 were included. A minimum follow up of 1 year was required. Patient data was extracted from electronic medical records and radiation treatment planning system. Pain intensity was evaluated utilizing a modified 0-4 Barrow Neurological Institute (BNI) pain intensity score, and then dichotomized where BNI score 0-2 represented response to treatment and BNI score 3-4 represented no response. Statistical analysis was conducted with a linear regression model accounting for race, gender, prior pain, pain distribution including laterality and branch involvement, medication regimen at time of treatment, previous radiation treatment, and prior procedures. Response was then compared between both modalities overall and within each sub-group with chi-square testing and linear regression. A total of 81 patients were identified, 14 patients were excluded due to lack of adequate follow-up, leaving 67 for analysis. 12 (17.9%) were male and, 55 (82.1%) were female. All patients were managed with medication prior to SRS treatment. 5 (7.5%) had rhizotomy and 13 (19.4) had microvascular decompression, and 8 (11.9%) had previous gamma-knife radiosurgery prior to SRS treatment at our institution. Of the 67 patients, 23 (34.3%) received frame-based gamma knife SRS, 44(65.7%) received frameless LINAC treatment. 58 (86.6%) radiation naïve patients received 90 Gy in 1 fraction, while out of the 9 who had previously had intracranial radiation treatment 7 (10.4%) received 70 Gy and 2 (3%) received 80 Gy all prescribed to 100% isodose line. All patients were treated with 4 mm cone. There was no significant difference in brainstem dose between these two techniques. Between LINAC-based or Gamma Knife modalities rate of pain control (77.3 % vs 82.6 %, respectively, p = 0.61) as well as toxicity in facial numbness (31.8% vs 21.7%, respectively, p = 0.38) showed no statistical difference. There was no statistically significant signal (p > 0.05) detected within the subgroups analyzed. The linear regression model also showed no significant difference. LINAC based frameless SRS provides comparable dosimetry and pain control for TN as compared to frame-based gamma knife treatment. It is a patient friendly solution for patients with TN.

Surface guided radiation therapy with an innovative open-face mask and mouth bite: patient motion management in brain stereotactic radiotherapy.

To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland-Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. The median of translation error between stages of the AlignRT positioning process was (0.03-0.07) cm, and the median of rotation error was (0.20-0.40)°, which were significantly better than those of the Fraxion positioning process (0.09-0.11) cm and (0.60-0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01cm, -0.07cm, 0.03cm, -0.30°, -0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10cm and 0.50°. The application of the SGRT with an innovative open-face mask and mouth bite device could achieve precision positioning accuracy and stability, and the accuracy of the AlignRT system exhibits excellent constancy with the CBCT gold standard. The non-coplanar radiation field monitoring can provide reliable support for motion management in fractional treatment.

Frameless versus frame-based stereotactic radiosurgery for intracranial arteriovenous malformations: A propensity-matched analysis.

The frameless linear accelerator (LINAC) based stereotactic radiosurgery (SRS) has been evolving with a reduction in patient discomfort. However, there was limited evidence comparing frame-based and frameless SRS for intracranial arteriovenous malformations (AVM). We aimed to compare the treatment outcomes between frame-based and frameless LINAC SRS. This retrospective cohort compared the outcomes of frame-based LINAC SRS (1998-2009) with frameless LINAC SRS (2010-2020). The primary outcome was the obliteration rate. The other outcomes included the neurological, radiological, and functional outcomes after SRS. A matched cohort was identified by propensity scores for further comparisons. A total of 65 patients were included with a mean follow-up time of 13.2years (158.5months). There were 40 patients in the frame-based group and 25 patients in the frameless group. The overall obliteration rate was comparable (Frame-based 82.5% vs Frameless 80.0%, p=0.310) and not significantly different over time (log-rank p=0.536). The crude post-SRS hemorrhage rate was 1.5% and the incidence was 0.3 per 100 person-years. There were 67.7% of patients with AVM obliteration without new persistent neurological deficits at the last visit and 56.9% of patients with AVM obliteration without any deficits (transient or persistent) during the entire follow-up period. Four patients (8.0%) developed late onset persistent adverse radiation effects (more than 96months after SRS) among 50 patients with more than 8-year surveillance. In the propensity-matched cohort of 42 patients, there was no significant difference in AVM obliteration (Frame-based vs Frameless, log-rank p=0.984). Frameless and frame-based LINAC SRS have comparable efficacy in intracranial AVM obliteration. A longer follow-up duration may further characterize the rate of late adverse radiation effects in frameless SRS.

Commissioning and clinical evaluation of the IDENTIFYTM surface imaging system for frameless stereotactic radiosurgery.

To commission and assess the clinical performance of a new commercial surface imaging (SI) system by analyzing intra-fraction motion from the initial cohort of patients treated with frameless stereotactic radiosurgery (fSRS). The IDENTIFYTM SI system was commissioned for clinical use on an Edge (Varian Medical Systems, Palo Alto, CA) linear accelerator. All patients who received intracranial radiotherapy with HyperArcTM (Varian Medical Systems, Palo Alto, CA) were immobilized with the EncompassTM (Qfix, Avondale, PA) thermoplastic mask and monitored for intra-fraction motion with SI. IDENTIFYTM log files were correlated with trajectory log files to correlate treatment parameters with SI-reported offsets. IDENTIFYTM reported offsets were correlated with gantry and couch angles to assess system performance for obstructed and clear camera field of view. Data were stratified by race to evaluate performance differences due to skin tone. All commissioning data were found to meet recommended tolerances. IDENTIFYTM was used to monitor intra-fraction motion on 1164 fractions from 386 patients. The median magnitude of translational SI reported offsets at the end of treatment was 0.27mm. SI reported offsets were shown to increase when camera pods are blocked by the gantry with larger increases seen at non-zero couch angles. With camera obstruction, the median magnitude of the SI reported offset was 0.50 and 0.80mm for White and Black patients, respectively. IDENTIFYTM performance during fSRS is comparable to other commercially available SI systems where offsets are shown to increase at non-zero couch angles and during camera pod blockage.

The clinical relevance of margins in frameless stereotactic radiosurgery for intact brain metastases: A randomized trial of 0 vs 2 mm margins.

TPS2080 Background: Stereotactic radiosurgery (SRS) is a commonly utilized treatment strategy for brain metastases which offers a relatively low rate of morbidity and high rate of local control. SRS delivers an ablative dose of radiation in a single session to a limited target volume while minimizing dose to surrounding normal tissue. Image-guided linear accelerator (LINAC)-based frameless SRS has enabled effective, safe delivery of high dose radiation without the discomfort and logistical complications associated with use of a rigid frame. Localization errors during frameless SRS vary depending on the specific LINAC configuration and immobilization technique. The clinical relevance of potential inaccuracies in localization with frameless SRS remains controversial. When employing frameless systems, many centers will account for set-up uncertainties by adding a circumferential margin of 1-3 mm around the GTV to create a planning target volume (PTV). This PTV expansion ensures adequate tumor coverage if target motion occurs, but exposes more normal brain tissue to radiation and may increase the risk of adverse events, chiefly radionecrosis. There is limited literature available to guide radiation oncologists on the appropriate choice of margin size, if any, for frameless SRS. There are no randomized data evaluating the safety and efficacy of omitting the margin entirely. Given the paucity of data examining margin extent and the potentially significant consequences for treatment efficacy and morbidity, we propose a phase II randomized prospective clinical trial evaluating 0 vs 2 mm marginal GTV to PTV expansions for treating patients with intact brain metastases with frameless SRS. Methods: Eligible patients will have brain metastases from solid tumors with ECOG performance status of 0-2 and life expectancy of >3 months. Patients must have 1 - 5 newly diagnosed well-circumscribed, measurable intraparenchymal brain metastases with maximum tumor diameter ≤3.0 cm. At least one lesion must be ≥ 0.5 cm in maximum diameter to be considered measurable. SRS will be delivered in a single fraction to either 20 Gy or 18 Gy dependent on tumor size. Importantly, PTV margin randomization is blinded and occurs after delineation of tumor volume by radiation oncologist to not bias contouring based on knowledge of margin randomization. This is two-armed multi-center phase II randomized controlled trial. The trial is powered to demonstrate non- inferiority of the experimental arm with regard to the primary endpoint of local PFS at 6 months and the superiority of the experimental arm with regard to the secondary endpoint of radionecrosis or pseudoprogression. We expect the total study duration, from the start of screening for the first participant until the end of follow-up for the last one, to be approximately six years. We plan to accrue 166 patients to this trial at all sites. Clinical trial information: NCT02747303 .

Mask dependency of the lacrimal gland dose under whole brain radiotherapy when the six-degrees of freedom couch is not available.

Dry eye syndrome has been recently reported in patients who underwent whole brain radiotherapy (WBRT). WBRT based on a couch with three-degrees of freedom (3D) can occasionally be performed in which the rotational head motion is not corrected. This study assessed the dependency of the rotational errors on the mask and the dose variation of the lens and lacrimal gland in WBRT patients. Translational and rotational setup errors were obtained at the first treatment with cone-beam CT (CBCT) for patients under WBRT and frameless stereotactic radiosurgery (SRS) (n=20 each) immobilized using a conventional WB mask and an SRS mask with a bite block, respectively. For the CT sets of SRS cases, WBRT plans were generated for the study. To simulate the rotational error, rotated CT images were created with each rotational error, on which initial WBRT plans were copied and doses were recalculated. The lens and lacrimal gland doses with and without rotation errors were compared. Despite similar translational setup errors for the two masks, the SRS mask showed a dramatic reduction in rotational errors compared to those of the WB mask. The errors varied within -2.9° to 2.9° and -1.2° to 0.7° for the WB and SRS masks, respectively. Accordingly, the SRS mask confined the change in the maximum lens dose, mean dose of the lacrimal gland, and lacrimal volume receiving 15Gy to one-third of those using the WB mask. When the six-degrees of freedom (6D) couch is not available, the frameless SRS mask is beneficial to WBRT for the faithful treatment as it was planned.

The Effectiveness and Toxicity of Frameless CyberKnife Based Radiosurgery for Parkinson's Disease-Phase II Study.

Frame-based stereotactic radiosurgery (SRS) has an established role in the treatment of tremor in patients with Parkinson's disease (PD). The low numbers of studies of frameless approaches led to our prospective phase 2 open-label single-arm clinical trial (NCT02406105), which aimed to evaluate the safety and efficacy of CyberKnife frameless SRS. Twenty-three PD patients were irradiated on the area of the thalamic ventral nuclei complex with gradually increasing doses of 70 to 105 Gy delivered in a single fraction. After SRS, patients were monitored for tremor severity and the toxicity of the treatment. Both subjective improvement and dose-dependent efficacy were analysed using standard statistical tests. The median follow-up was 23 months, and one patient died after COVID-19 infection. Another two patients were lost from follow-up. Hyper-response resulting in vascular toxicity and neurologic complications was observed in two patients irradiated with doses of 95 and 100 Gy, respectively. A reduction in tremor severity was observed in fifteen patients, and six experienced stagnation. A constant response during the whole follow-up was observed in 67% patients. A longer median response time was achieved in patients irradiated with doses equal to or less than 85 Gy. Only two patients declared no improvement after SRS. The efficacy of frameless SRS is high and could improve tremor control in a majority of patients. The complication rate is low, especially when doses below 90 Gy are applied. Frameless SRS could be offered as an alternative for patients ineligible for deep brain stimulation; however, studies regarding optimal dose are required.

Dosimetric Analysis of Intra-Fraction Motion Detected by Surface-Guided Radiation Therapy During Linac Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) immobilization with an open face mask is more comfortable and less invasive than frame based, but concerns about intrafraction motion must be addressed. Surface-guided radiation therapy (SGRT) is an attractive option for intrafraction patient monitoring because it is continuous, has submillimeter accuracy, and uses no ionizing radiation. The purpose of this study was to investigate the dosimetric consequences of uncorrected intrafraction patient motion detected during frameless linac-based SRS. Fifty-five SRS patients were monitored during treatment using SGRT between January 1, 2017, and September 30, 2020. If SGRT detected motion >1 mm, imaging was repeated and the necessary shifts were made before continuing treatment. For the 25 patients with intrafraction 3-dimensional vector shifts of ≥1 mm, we moved the isocenter in the planning system using the translational shifts from the repeat imaging and recalculated the plans to determine the dosimetric effect of the shifts. Planning target volume (PTV) coverage, minimum gross tumor volume (GTV) dose (relative and absolute), and normal brain V12 were evaluated. Wilcoxon signed rank tests were used to compare planned and simulated dosimetric parameters and median 2 sample tests were used to investigate these differences between cone and multileaf collimator (MLC) plans. For simulated plans, V12 increased by a median of 0.01 cc (P=.006) and relative GTV minimum dose and PTV coverage decreased by a median of 15.8% (P < .001) and 10.2 % (P < .001), respectively. Absolute minimum GTV dose was found to be significantly lower in the simulated plans (P < .001). PTV coverage decreased more for simulated cone plans than for simulated MLC plans (11.6% vs 4.7%, P=.011) but median V12 differences were found to be significantly larger for MLC plans (-0.34 cc vs -0.01 cc, P=.011). Differences in GTV minimum dose between cone and MLC plans were not statistically significant. SGRT detected clinically meaningful intrafraction motion during frameless SRS, which could lead to large underdoses and increased normal brain dose if uncorrected.

Stereotactic radiosurgery for recurrent pediatric brain tumors: clinical outcomes and toxicity.

Recurrence of brain tumors in children after the initial course of treatment remains a problem. This study evaluated the efficacy and safety of reirradiation using stereotactic radiosurgery (SRS) in patients with recurrent pediatric primary brain tumors. This IRB-approved retrospective review included pediatric patients with recurrent primary brain tumors treated at Stanford University from 2000 to 2019 using frameless SRS. Time to local failure (LF) and distant intracranial failure (DIF) were measured from the date of SRS and analyzed using competing risk analysis. Overall survival (OS) and progression-free survival (PFS) were analyzed with the Kaplan-Meier method. In total, 37 patients aged 2-24 years (median age 11 years at recurrence) were treated for 48 intracranial tumors. Ependymoma (38%) and medulloblastoma (22%) were the most common tumor types. The median (range) single fraction equivalent dose of SRS was 16.4 (12-24) Gy. The median (range) follow-up time was 22.9 (1.5-190) months. The median OS of all patients was 36.8 months. Eight of 40 (20%) lesions with follow-up imaging locally recurred. The 2-year cumulative incidence of LF after reirradiation with SRS was 12.8% (95% CI 4.6%-25.4%). The 2-year cumulative incidence of DIF was 25.3% (95% CI 12.9%-39.8%). The median PFS was 18 months (95% CI 8.9-44). Five (10.4%) patients developed toxicities potentially attributed to SRS, including cognitive effects and necrosis. Reirradiation using SRS for recurrent pediatric brain tumors appears safe with good local control. Innovations that improve overall disease control should continue because survival outcomes after relapse remain poor.

Feasibility of fractionated gamma knife radiosurgery in the management of newly diagnosed Glioblastoma

BackgroundGlioblastoma (GBM) is the most common primary malignant brain tumor in adults, with overall survival remaining poor despite ongoing efforts to explore new treatment paradigms. Given these outcomes, efforts have been made to shorten treatment time. Recent data report on the safety of CyberKnife (CK) fractionated stereotactic radiosurgery (SRS) in the management of GBM using a five-fraction regimen. The latest Gamma Knife (GK) model also supports frameless SRS, and outcomes using GK SRS in the management of primary GBM have not yet been reported.ObjectiveTo report on the feasibility of five-fraction SRS with the GammaKnife ICON in the management of newly diagnosed GBM.MethodsIn this single institutional study, we retrospectively reviewed all patients from our medical center from January 2017 through December 2021 who received fractionated SRS with Gamma Knife ICON for newly diagnosed GBM. Patient demographics, upfront surgical margins, molecular subtyping, radiation treatment volumes, systemic therapies, and follow-up imaging findings were extracted to report on oncologic outcomes.ResultsWe identified six patients treated within the above time frame. Median age at diagnosis was 73.5 years, 66% were male, and had a median Karnofsky Performance Status (KPS) of 70. All tumors were IDH wild-type, and all but one were MGMT methylated and received concurrent temozolomide (TMZ). Within this group, progression free survival was comparable to that of historical data without significant radiation-induced toxicities.ConclusionGamma Knife ICON may be discussed as a potential treatment option for select GBM patients and warrants further investigation in the prospective setting.

Frameless Co-Registration of Biplane 2D Digital Subtraction Angiography Whole Frames and 3D Rotational Angiography-Based Cone-Beam Computed Tomography Angiogram on Dedicated Software for Stereotactic Radiosurgery of Cranial Vascular Malformations.

Purpose: Given its high spatial resolution and vasculature selectivity, the cone-beam computed tomography (CT) angiography (CBCTA) image acquired by selective 3D rotational angiography (3DRA) is the most suitable 3D image for the target definition of stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs). Furthermore, the relatively low temporal resolution of 3DRA-based CBCTA can be complemented by the stereotactic co-registration of orthogonally paired 2D dynamic digital subtraction angiography (2D-DSA). The integration of 2D-DSA, which is usually limited to one or a few frames for each projection, into CBCTA and/or planning CT can be achieved only by catheter-directed angiography on the day of SRS via a dedicated image localizer under rigid frame fixation to the skull, which imposes substantial burdens on patients. This study aimed to demonstrate a novel, convenient, and significantly less invasive method for the frameless co-registration of biplane 2D-DSA whole frames and CBCTA on commercially available dedicated software, namely, Brainlab® Elements (Brainlab AG, Munich, Germany), and present its prerequisite for successful image fusion.Technical Report: Elements have afforded the following functionality: A 3D vasculature image is automatically extracted as a floating image from any 3D image series containing vascular details and then subsequently co-registered manually and automatically to a selected frame pair of 2D-DSA with a six-degree-of-freedom rigid registration. As a preclinical feasibility study, two anonymous image datasets from patients harboring cerebral AVM and transverse-sigmoid (TS) DAVF were used to verify the accuracy and practicality of Elements for the frameless co-registration of 2D/3D vascular images, particularly on the assumption of clinical workflow for the target delineation of SRS planning. The use of ordinary unsubtracted CBCTA resulted in the insufficient extraction of abutting vessels or vessels that are in close proximity to bony structures, particularly in the case of TS-DAVF, where the fistulous pouch and the affected venous sinuses were adjacent to the cranial bone. By contrast, the amount and selectivity of vasculatures and the accuracy of subsequent image fusion were significantly improved from the subtracted CBCTA. The integration of CBCTA into dynamic 2D-DSA allowed the simultaneous review of both image information by sharing any concerning point and 2D or 3D structures under a common 3D coordinate.Conclusions: Elements enable the clinically useful frameless co-registration of biplane 2D-DSA whole frames into CBCTA, for which the routine acquisition of both subtracted and unsubtracted CBCTA axial images for ordinary diagnostic purposes is an indispensable prerequisite for successful image fusion and further widespread application. This frameless integration of the 2D/3D angiogram would dramatically enhance both the frame-based and frameless SRS workflow and circumstances by allowing users to forward SRS planning well in advance before SRS, along with the omission of invasive angiography on the day of SRS, and would broaden the implementation of frameless SRS. Furthermore, the comprehensive alternating interactive review of the 2D/3D integrated angiogram leads to a more in-depth quasi-4D understanding of the affected angioarchitectures compared with the separate viewing of each image.

Single-isocenter stereotactic radiosurgery for multiple brain metastases: Impact of patient misalignments on target coverage in non-coplanar treatments

Frameless single-isocenter non-coplanar stereotactic radiosurgery (SRS) for patients with multiple brain metastases is a treatment at high geometrical complexity. The goal of this study is to analyze the dosimetric impact of non-coplanar image guidance with stereoscopic X-ray imaging. Such an analysis is meant to provide insights on the adequacy of safety margins, and to evaluate the benefit of imaging at non-coplanar configurations.The ExacTrac® (ET) system (Brainlab AG, Munich, Germany) was used for stereoscopic X-ray imaging in frameless single-isocenter non-coplanar SRS for multiple brain metastases. Sub-millimeter precision was found for the ET-based pre-treatment setup, whereas a degradation was noted for non-coplanar treatment angles. Misalignments without intra-fractional positioning corrections were reconstructed in 6 degrees of freedom (DoF) to resemble the situation without non-coplanar image guidance.Dose recalculation in 20 SRS patients with applied positioning corrections did not reveal any significant differences in D98% for 75 planning target volumes (PTVs) and gross tumor volumes (GTVs). For recalculation without applied positioning corrections, significant differences (p<0.05) were reported in D98% for both PTVs and GTVs, with stronger effects for small PTV volumes. A worst-case analysis at increasing translational and rotational misalignment revealed that dosimetric changes are a complex function of the combination thereof.This study highlighted the important role of positioning correction with ET at non-coplanar configurations in frameless single-isocenter non-coplanar SRS for patients with multiple brain metastases. Uncorrected patient misalignments at non-coplanar couch angles were linked to a significant loss of PTV coverage, with effects varying according to the combination of single DoF and PTV geometrical properties.

AAPM task group report 302: Surface-guided radiotherapy.

The clinical use of surface imaging has increased dramatically, with demonstrated utility for initial patient positioning, real‐time motion monitoring, and beam gating in a variety of anatomical sites. The Therapy Physics Subcommittee and the Imaging for Treatment Verification Working Group of the American Association of Physicists in Medicine commissioned Task Group 302 to review the current clinical uses of surface imaging and emerging clinical applications. The specific charge of this task group was to provide technical guidelines for clinical indications of use for general positioning, breast deep‐inspiration breath hold treatment, and frameless stereotactic radiosurgery. Additionally, the task group was charged with providing commissioning and on‐going quality assurance (QA) requirements for surface‐guided radiation therapy (SGRT) as part of a comprehensive QA program including risk assessment. Workflow considerations for other anatomic sites and for computed tomography simulation, including motion management, are also discussed. Finally, developing clinical applications, such as stereotactic body radiotherapy (SBRT) or proton radiotherapy, are presented. The recommendations made in this report, which are summarized at the end of the report, are applicable to all video‐based SGRT systems available at the time of writing.

Characterization and commissioning of a Leksell Gamma Knife ICON system for framed and frameless stereotactic radiosurgery.

PurposeThe Leksell Gamma Knife Icon unit (IU) was introduced recently as an upgrade to the Perfexion unit (PU) at our Gamma Knife practice. In the current study, we sought mainly to characterize dosimetry and targeting accuracy of the IU treatment deliveries using both invasive frame and frameless treatment workflows.MethodsRelative output factors were measured by delivering single‐shot 4, 8 and 16 mm radiation profiles in the manufacturer's acrylonitrile butadiene styrene spherical phantom in coronal and sagittal planes using EBT3 film. Resultant dosimetry was compared with the manufacturer's dose calculation and derived output factors were compared with the manufacturer's published value. Geometric consistency of stereotactic coordinates based on cone‐beam computed tomography (CBCT) versus the traditional conventional CT‐based method was characterized using a rigid phantom containing nine fiducial indicators over four separate trials. End‐to‐end (E2E) testing using EBT3 film was designed to evaluate both dosimetric and geometric accuracy for hypothetical framed and frameless workflows.ResultsRelative output factors as measured by the manufacturer were independently confirmed using EBT3 film measurements to within 2%. The mean 3D radial discrepancy in stereotactic space between CBCT and CT‐based definition over the sampled locations in our rigid geometry phantom was demonstrated to be between 0.40 mm and 0.56 mm over the set of trials, larger than prior reported values. E2E performed in 2D demonstrates sub‐mm (and typically < 0.5 mm) accuracy for framed and frameless workflows; geometric accuracy of framed treatments using CBCT‐defined stereotactic coordinates was shown to be slightly improved in comparison with those defined using conventional CT. Furthermore, in phantom, frameless workflows exhibited better accuracy than framed workflows for fractionated treatments, despite large magnitudes of introduced interfraction setup error. Accuracy of dosimetric delivery was confirmed in terms of qualitative comparisons of dose profiles and in terms of 2D gamma pass rates based on 1%/1 mm criteria.ConclusionThe IU was commissioned for clinical use of frameless and framed treatment protocols. The present study outlines an extensive E2E methodology for confirmation of dosimetric and geometric treatment accuracy.

Tolerability and Stability of Mask Fixation in Gamma Knife Stereotactic Radiosurgery: Predictors of Treatment Interruptions

Background. Frameless fixation with a thermoplastic mask is an alternative to traditional frame-based immobilization for Gamma-Knife stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). However, interruptions during beam-on time can significantly prolong treatment delivery, impacting patient experience and unit workflow. Aim. We investigated clinical and technical predictors of treatment interruptions, and the phases of treatment during which interruptions are most likely to occur. Methods. Patients undergoing frameless Gamma Knife SRS or FSRT in 2020 were retrospectively reviewed. Clinical parameters were extracted from electronic medical records. Dosimetric and treatment interruption data were obtained from Gamma Knife treatment reports. Univariate and multivariate analyses analyzed technical and clinical predictors of treatment interruptions. Results. Our cohort included 84 patients receiving 141 fractions encompassing 255 lesions. 49/84 (58.3%) were female, 79/84 (94.0%) had brain metastases, 49/84 (58.3%) were taking dexamethasone and 30/84 (35.7%) used analgesics. 89/106 (84.0%) courses were single fractions. Mean planned beam-on time was 37.1 minutes (range 7.1-118.8 min) versus a total bed time of 64.9 minutes (range 15-252min) per fraction. 64.5% (91/141) of fractions were interrupted at least once; 12/141 fractions were paused 20 times or more, with a maximum 54 pauses. The mean number of pauses per quartile decreased the further the patient proceeded in beam-on time, and patients receiving first lifetime cranial radiation paused more often than during subsequent fractions. At least one pause occurred in 100% of fractions with a planned beam-on time exceeding 60 minutes. Planned beam-on time, number of gating events and high-definition motion management alarms significantly correlated with total number of pauses on multivariate analysis (all p&lt;0.0001); these three factors, along with prep time and number of operator-initiated pauses, predicted total time on the Gamma Knife couch (all p&lt;0.0001). Clinical factors, medication use, and prior SRS/FSRT were not predictive of pauses. Conclusions. Planned beam-on time, number of gating events and high-definition motion management alarms significantly predicted likelihood of interruptions during frameless Gamma Knife SRS/FSRT. These factors should be considered in selection of immobilization method, especially if exceeding 60 minutes.

Cyberknife Radiosurgery for the Treatment of Head and Neck Cancer: A Systematic Review.

Cyberknife radiosurgery is a frameless stereotactic robotic radiosurgery which has shown to deliver better treatment outcomes in the treatment of advanced head and neck (H&N) carcinomas, especially in previously irradiated and recurrent cases. The aim of the study was to perform a systematic review of the available data on the outcomes of Cyberknife radiosurgery for treatment of head and neck cancer and to evaluate its collective outcomes. This systematic review was registered with the university with the registration no. FRP/2019/63 and was approved by the Institutional Review Board (RC/IRB/2019/132). Literature search was performed in the following: PubMed, Science direct, SciELO, MyScienceWork, Microsoft Academ EMBASE, Directory of Open Access Journals, and Cochrane databases with the keywords “Cyberknife,” “oral cancer,” “oropharyngeal cancer,” and “head and neck cancer” and data was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The records identified were 147 manuscripts. Excluded articles included 5 duplicate articles, 33 abstracts, 101 full text articles due to being off-topic, case reports, review, non-English, 1 survey, and 2 other articles containing data extracted from a main study which was already included. A total of 5 articles were evaluated for qualitative synthesis. The mean dose of Cyberknife radiosurgery delivered for previously irradiated recurrent H&N carcinoma patients was 34.57 Gy, with a mean sample size of 5 studied during the period of 2000 to 2016. The available evidence from the systematic review indicates that Cyberknife can be an efficacious treatment option for recurrent previously irradiated H&N carcinoma, especially for nonresectable tumors. There is paucity of homogenous data and studies in this arena; hence, meta-analysis could not be performed. Further standardized studies are essential, especially where the treatment of H&N carcinoma is considered.

Technical note: Personalized treatment gating thresholds in frameless stereotactic radiosurgery using predictions of dosimetric fidelity and treatment interruption.

Gamma Knife Icon (GKI) enables a user-defined gating threshold for intrafraction motion during stereotactic radiosurgery (SRS). An optimal threshold would ensure dosimetric fidelity of the planned distribution and minimize treatment time extension by gating. A prediction of motion characteristics for a patient based on a retrospective database of motion traces could be beneficial to evaluating the choice of gating threshold. A short acquisition of motion may help to define a personalized threshold that balances dosimetric accuracy and treatment length. This study aims to evaluate the performance of a prediction of motion and the resultant dosimetric consequences for a range of motion gating thresholds. A database of 2552 motion traces (776 patients) was analyzed using previously published methods to characterize patient intrafraction motion on the GKI. For a selection of six fractionated SRS patient cases (two patients with single brain metastasis, four vestibular schwannomas), a 10-min sample of motion was used to classify motion and identify traces in the database with similar metrics. The similar motion traces were used to perform a predictive reconstruction of the selected patient's delivered dose for a range of motion thresholds. The remaining fractions were reconstructed and compared to that predicted. From the six cases, 26 fractions were used to predict the number of interruptions (n=26), change in target coverage (n=26), and change in brainstem maximum dose (vestibular cases only, n=20). The difference between mean predicted and reconstructed values was compared for accuracy. The difference between mean prediction and reconstructed values was 0.32 ± 0.38% in target coverage, 2.36 ± 5.06 interruptions, and 0.15 ± 0.24Gy for the brainstem maximum dose. Sixty-seven of the 72 predictions (26 coverage, 26 interruptions, and 20 brainstem maximum dose) were within one standard deviation of the predicted mean. Large databases of motion traces were used to characterize patient performance and predict motion performance. Dosimetric deterioration due to motion and extension of treatment duration can be predicted in some cases using only a short acquisition of motion and the treatment plan. This reconstruction may provide benefit in generating a patient-specific motion threshold.