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Background: Robotic radiosurgery treatments allow for precise non-coplanar beam delivery by utilizing a robot equipped with a linac that traverses through a set of predetermined nodes. High quality treatment plans can be produced but treatment times can grow large, with one substantial component being the robot traversal time., Purpose: The aim of this study is to reduce the treatment time for robotic radiosurgery treatments by introducing algorithms for reducing the robot traversal time. The algorithms are integrated into a commercial treatment planning system., Methods: First, an optimization framework for robotic radiosurgery planning is detailed, including a heuristic optimization method for node selection. Second, two methods aimed at reducing the traversal time are introduced. One utilizes a centrality measure focusing on the structure of the node network, while the other is based on the direct computation of traversal times during optimization. A comparison between plans with and without the time-reducing algorithms is made for three brain cases and one liver case with basis in treatment time, plan quality, monitor units, and network structure of the selected nodes., Results: Large decreases in traversal times are obtained by the traversal time reducing algorithms, with reductions of up to 49 % in the brain cases and 31 % in the liver case. The resulting reductions in treatment times are up to 30 % and 13 %, respectively. Small differences in plan quality are observed, with similar dose-volume histograms, dose distributions, and conformity/gradient indices., Conclusions: The total treatment time of the robotic radiosurgery treatments can be reduced by selecting nodes with more efficient robot traversal paths, while maintaining plan quality., (© 2024 American Association of Physicists in Medicine.)

Purpose: Although emerging clinical evidence supports robotic radiosurgery as a highly effective treatment option for renal cell carcinoma (RCC) less than 4 cm in diameter, delivery uncertainties and associated target volume margins have not been studied in detail. We assess intrafraction tumor motion patterns and accuracy of robotic radiosurgery in renal tumors with real-time respiratory tracking to optimize treatment margins., Methods: Delivery log files from 165 consecutive treatments of RCC were retrospectively analyzed. Five components were considered for planning target volume (PTV) margin estimation: (a) The model error from the correlation model between patient breath and tumor motion, (b) the prediction error from an algorithm predicting the patient breathing pattern, (c) the targeting error from the treatment robot, (d) the inherent total accuracy of the system for respiratory motion tracking, and (e) the margin required to cover potential target rotation, simulated with PTV rotations up to 10°., Results: The median tumor motion was 10.5 mm, 2.4 mm and 4.4 mm in the superior-inferior, left-right, and anterior-posterior directions, respectively. The root of the sum of squares of all contributions to the system's inaccuracy results in a minimum PTV margin of 4.3 mm, 2.6 mm and 3.0 mm in the superior-inferior, left-right and anterior-posterior directions, respectively, assuming optimal fiducial position and neglecting target deformation., Conclusions: We have assessed kidney motion and derived PTV margins for the treatment of RCC with robotic radiosurgery, which helps to deliver renal treatments in a more consistent manner and potentially further improve outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Image-guided radiation-therapy (IGRT)-based robotic radiosurgery using magnetic resonance imaging (MRI)-only simulation could allow for improved target definition with highly conformal radiotherapy treatments. Fiducial marker (FM)-based alignment is used with robotic radiosurgery treatments of sites such as the prostate because it aids in accurate target localization. Synthetic CT (sCT) images are generated in the MRI-only workflow but FMs used for IGRT appear as signal voids in MRIs and do not appear in MR-generated sCTs, hindering the ability to use sCTs for fiducial-based IGRT., Purpose: In this study we evaluate the fiducial tracking accuracy for a novel artificial fiducial insertion method in sCT images that allows for fiducial marker tracking in robotic radiosurgery, using MRI-only simulation imaging (MRI-only workflow)., Methods: Artificial fiducial markers were inserted into sCT images at the site of the real marker implantation as visible in MRI. Two phantoms were used in this study. A custom anthropomorphic pelvis phantom was designed to validate the tracking accuracy for a variety of artificial fiducials in an MRI-only workflow. A head phantom containing a hidden target and orthogonal film pair inserts was used to perform end-to-end tests of artificial fiducial configurations inserted in sCT images. The setup and end-to-end targeting accuracy of the MRI-only workflow were compared to the computed tomography (CT)-based standard. Each phantom had six FMs implanted with a minimum spacing of 2 cm. For each phantom a bulk-density sCT was generated, and artificial FMs were inserted at the implantation location. Several methods of FM insertion were tested including: (1) replacing HU with a fixed value (10000HU) (voxel-burned); (2) using a representative fiducial image derived from a linear combination of fiducial templates (composite-fiducial); (3) computationally simulating FM signal voids using a digital phantom containing FMs and inserting the corresponding signal void into sCT images (simulated-fiducial). All tests were performed on a CyberKnife system (Accuray, Sunnyvale, CA). Treatment plans and digital-reconstructed-radiographs were generated from the original CT and sCTs with embedded fiducials and used to align the phantom on the treatment couch. Differences in the initial phantom alignment (3D translations/rotations) and tracking parameters between CT-based plans and sCT-based plans were analyzed. End-to-end plans for both scenarios were generated and analyzed following our clinical protocol., Results: For all plans, the fiducial tracking algorithm was able to identify the fiducial locations. The mean FM-extraction uncertainty for the composite and simulated FMs was below 48% for fiducials in both the anthropomorphic pelvis and end-to-end phantoms, which is below the 70% treatment uncertainty threshold. The total targeting error was within tolerance (<0.95 mm) for end-to-end tests of sCT images with the composite and head-on simulated FMs (0.26, 0.44, and 0.35 mm for the composite fiducial in sCT, head-on simulated fiducial in sCT, and fiducials in original CT, respectively., Conclusions: MRI-only simulation for robotic radiosurgery could potentially improve treatment accuracy and reduce planning margins. Our study has shown that using a composite-derived or simulated FM in conjunction with sCT images, MRI-only workflow can provide clinically acceptable setup accuracy in line with CT-based standards for FM-based robotic radiosurgery., (© 2023 American Association of Physicists in Medicine.)

Objective: To investigate the long-term safety and efficacy of high-dose radiotherapy after 3D-printed vertebral body implantation in the treatment of spinal tumors., Methods: Thirty-three participants were recruited between July 2017 and August 2019. 3D-printed vertebral bodies were implanted in each participant, followed by postoperative robotic stereotactic radiosurgery at a dose of 35-40 Gy/5f. The tolerance of the 3D-printed vertebral body and the participant to the high-dose radiotherapy were evaluated. In addition, the local control of tumor and the local progression-free survival of the study participants following 3D-printed vertebral body implantation and high-dose radiotherapy were measured as indexes of effectiveness., Results: Of the 33 participants included in the study, 30, including three participants (10%) with esophagitis of grade 3 or above and two participants (6.7%) with advanced radiation nerve injury, successfully underwent postoperative high-dose radiotherapy. The median follow-up was 26.7 months, and IQR was 15.9 months. Most participants had primary bone tumors with 27 cases (81.8%), and the rest had bone metastases in six cases (18.2%). After high-dose radiotherapy, the 3D-printed vertebrae maintained good vertebral stability and exhibited histocompatibility, without implant fractures. The local control rates were 100%, 88%, and 85% 6 months, 1 year, and 2 years after high-dose radiotherapy, respectively. Tumors recurred in four participants (12.1%) during the follow-up period. The median local progression-free survival after treatment was 25.7 months, with a range of 9.6-33.0 months., Conclusion: High-dose radiotherapy for spinal tumors after 3D-printed vertebral body implantation is feasible, elicits low toxicity, and yields satisfactory tumor control., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Cyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion correction. Although RRS appears to cause more radiation necrosis (RN), the radiometabolic changes after RRS have not been fully clarified. 18 F-FET-PET/CT is used to differentiate recurrent tumor (RT) from RN after radiosurgery when MRI findings are indecisive. We explored the usefulness of dynamic parameters derived from 18 F-FET PET in differentiating RT from RN after Cyberknife treatment in a single-center study population., Methods: We retrospectively identified brain tumor patients with static and dynamic 18 F-FET-PET/CT for suspected RN after Cyberknife. Static (tumor-to-background ratio) and dynamic PET parameters (time-activity curve, time-to-peak) were quantified. Analyses were performed for all lesions taken together (TOTAL) and for brain metastases only (METS). Diagnostic accuracy of PET parameters (using mean tumor-to-background ratio >1.95 and time-to-peak of 20 min for RT as cut-offs) and their respective improvement of diagnostic probability were analyzed., Results: Fourteen patients with 28 brain tumors were included in quantitative analysis. Time-activity curves alone provided the highest sensitivities (TOTAL: 95%, METS: 100%) at the cost of specificity (TOTAL: 50%, METS: 57%). Combined mean tumor-to-background ratio and time-activity curve had the highest specificities (TOTAL: 63%, METS: 71%) and led to the highest increase in diagnosis probability of up to 16% p. - versus 5% p. when only static parameters were used., Conclusions: This preliminary study shows that combined dynamic and static 18 F-FET PET/CT parameters can be used in differentiating RT from RN after RRS., (Copyright © 2022. Published by Elsevier Ltd.)

Quantitative retrospective analysis of the normal lung irradiation due to the variations of the ITV volume based on the techniques used for upper lobe (UL), mid lobe (ML), and lower lobe (LL) lung tumours when used with 2-view, 1-view, 0-view based LOT technique on Cyberknife, AveIP on Helical Tomotherapy, and DIBH on VMAT systems. In the treatment of lung tumours, patients medically inoperable or those who are unwilling to undergo surgery have the option to be treated using radiation therapy. There are many motion control techniques available for the treatment of the moving target, such as movement encompassment, respiratory gating, breath-hold, motion reduction, and tumour monitoring. ITV generation is dependent on technique and hence the volume of the PTVs will differ based on the technique used. This study aimed to determine the influence of these ITVs on the irradiated normal lung volume for UL, ML, and LL lung tumours for 23 patients. The mean difference in the PTV volumes generated with the 0-view technique was significant with that of 2-view and DIBH techniques (p-value < 0.04). The mean difference in the PTV volumes generated by 2-view and DIBH was small for UL, ML, and LL tumours. V 5 of the combined lung with the 0-view method was 5% compared to the 2-view method for UL tumours (p-value = 0.04) and the same was 9.5%, and 16.8% for ML and LL tumours (p-value < 0.04). In contrast to all other techniques, lung volume parameters V 5 , V 10 , V 20, and V 30 for the 0-view technology were consistently higher irrespective of the tumour location in the lung. The observed maximum mean lung dose (MLD) was 6.2 Gy ± 2.7 Gy with the 0-view technique and the minimum was 3.85 Gy ± 1.75 Gy with the DIBH technique. The difference in MLD between DIBH and 2-view was negligible (p-value = 0.67). The MLD increased for LL tumours from 4 Gy to 6.5 Gy from the 2-view to 0-view technique (p-value = 0.009). There was a significant increase in MLD for LL tumours with the 0-view technique compared to AveIP (1.9 Gy, p-value = 0.04) and DIBH (2.0 Gy, p-value = 0.003) technique. For ML and UL tumours, except for 0-view and 1-view, the difference in the MLD between the rest of the methods was not significant (p-value > 0.11). In the treatment of lung tumour patients with SBRT, this study has demonstrated 2-view with Cyberknife and DIBH with VMAT treatment techniques have optimal normal lung tissue sparing. There was a significant increase in the average lung volume receiving 5%,10%, 20%, and 30% dose when comparing the 1-view, 0-view, AveIP, and DIBH techniques to the 2-view technique. However, DIBH with VMAT was dosimetrically advantageous for ML and LL tumours, while providing significantly shorter treatment times than any other technique studied., (© 2021. Australasian College of Physical Scientists and Engineers in Medicine.)

Background: This is a prospective study evaluating the role of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) in Indian patients suffering from hepatocellular carcinoma with portal vein thrombosis (HCC-PVT)., Methods: Patients with inoperable HCC-PVT, good performance score (PS), and liver function are accrued for treatment on CK (version M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring, and the gross tumor volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per-risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy, and the duodenum max of ≤24 Gy)., Results: Seventy-two HCC-PVT accrued till date (mean age 63 years [38-76 years], 96% male; Child-Pugh [CP] A 84%, B 9%; Barcelona-Clinic Liver Cancer [BCLC] C 96%; PS0-1: 80%, Karnofsky performance score [KPS]>70: 88%; co-morbidities 42%; infective 12%, alcohol intake 31%, adjuvant sorafenib 39%). CP scores 5, 6, 7, and 8 were in 35%, 32%, 8%, and 18%, respectively. Focal disease with portal vein thrombus (PVT) in 21%, liver involvement >50% and <50% in 46% and 32%. Liver cancer study group of Japan staging-based portal vein invasion VP2, VP3, and VP4 in 22%, 29%, and 40%. Cancer of the Liver Italian Programm (CLIP) scores 1, 2, 3, 4, and 5 were in 8%, 26%, 31%, 26%, and 7%, respectively. Mean follow-up was 7.3 months (median 6 months, standard deviation [SD] 6; range 3-30 months). Mean actuarial overall survival (OS) was 11.4 months (SE 1.587; 95% CI: 8-14.2 months). Six months and 12 months actuarial OS 55% and 38%, respectively. At last follow-up, 25/69 (36%) were alive and 44/69 (64%) were dead. Among 54 patients evaluated for response assessment, 23 (30%) had radiological confirmed PVT response, 1 (3%) had response of IVC thrombus, and 30 (42%) had no or minimal response to SBRT. Actuarial OS in responders and non-responders were 14.4 months (95% CI 9.4-19.2) and 7.4 months (95% CI 4.9-9.7), p-value: 0.022. Six and 12 months survival in responders and non-responders were 65.7% and 37% and 49% and 24.6%, respectively. Post-SBRT, 4 (12%) patients underwent transarterial chemoembolization (TACE) 3 patients (8%) and 1 patient (4%) transarterial radioembolization (TARE). Post-CK, (<4 weeks) 2 patients (4%) had decompensation., Conclusions: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT., (© 2021. Indian Society of Gastroenterology.)

Purpose: Vasoproliferative tumours (VPT) are a rare but benign entity that can lead to severe visual acuity deterioration. There is no standard of care, and depending on the degree of clinical features, including tumour size and dissemination, visual acuity and subretinal fluid, treatment options include observation, cryotherapy and brachytherapy. Particularly in larger tumours, brachytherapy has advantages over other options, although higher radiation doses and the need for surgical application are disadvantages of this otherwise effective treatment option. CyberKnife radiosurgery might represent an alternative therapeutic option as no surgical intervention is needed and radiation doses are lower., Methods: All patients diagnosed with vasoproliferative tumors who were treated with CyberKnife radiosurgery with a minimum follow-up time of 12 months were included in this case series. We recorded visual acuity, number of lesions, central retinal thickness with optical coherence tomography (OCT) and reflectivity using A-scan standardizes echography every three months., Results: A total of four patients with a median age of 34 years (range: 24 - 51) who were observed over an average of 26.5 months (range: 17 - 49 months) matched our inclusion criteria. We appreciated stabilization or increase in visual acuity in all four patients and a regression in tumour thickness with subsequent increase in internal reflectivity as a marker of increasing fibrosis., Conclusion: We observed good visual and functional outcome following CyberKnife therapy for VPT. We believe that further studies should be pursued to evaluate CyberKnife therapy for the treatment of VPT not treatable with cryo- or lasertherapy., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Robotic radiosurgery offers the flexibility of a robotic arm to enable high conformity to the target and a steep dose gradient. However, treatment planning becomes a computationally challenging task as the search space for potential beam directions for dose delivery is arbitrarily large. We propose an approach based on deep learning to improve the search for treatment beams., Methods: In clinical practice, a set of candidate beams generated by a randomized heuristic forms the basis for treatment planning. We use a convolutional neural network to identify promising candidate beams. Using radiological features of the patient, we predict the influence of a candidate beam on the delivered dose individually and let this prediction guide the selection of candidate beams. Features are represented as projections of the organ structures which are relevant during planning. Solutions to the inverse planning problem are generated for random and CNN-predicted candidate beams., Results: The coverage increases from 95.35% to 97.67% for 6000 heuristically and CNN-generated candidate beams, respectively. Conversely, a similar coverage can be achieved for treatment plans with half the number of candidate beams. This results in a patient-dependent reduced averaged computation time of 20.28%-45.69%. The number of active treatment beams can be reduced by 11.35% on average, which reduces treatment time. Constraining the maximum number of candidate beams per beam node can further improve the average coverage by 0.75 percentage points for 6000 candidate beams., Conclusions: We show that deep learning based on radiological features can substantially improve treatment plan quality, reduce computation runtime, and treatment time compared to the heuristic approach used in clinics., (© 2020 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: When a lung lesion is detected by only one couple of X-ray tube and image detector integrated with CyberKnife®, the fiducial-less tracking is limited to 1-view (34% of lung treatments at Centro Diagnostico Italiano). The aim of the study was mainly to determine the margin needed to take into account the localization uncertainty along the blind view (out-of-plane direction)., Methods: 36 patients treated in 2-view tracking modality (127 fractions in total) were included in the study. The actual tumor positions were determined retrospectively through logfile analysis and were projected onto 2D image planes. In the same plots the planned target positions based on biphasic breath-hold CT scans were represented preserving the metric with respect to the imaging center. The internal margin necessary to cover in out-of-plane direction the 95% of the target position distribution in the 95% of cases was calculated by home-made software in Matlab®. A validation test was preliminarily performed using XLT Phantom (CIRS) both in 2-view and 1-view scenarios., Results: The validation test proved the reliability of the method, in spite of some intrinsic limitations. Margins were estimated equal to 5 and 6 mm for targets in upper and lower lobe respectively. Biphasic breath-hold CT led to underestimate the target movement in the hypothetical out-of-plane direction. The inter-fractional variability of spine-target distance was an important source of uncertainty for 1-view treatments., Conclusion: This graphic comparison method preserving metric could be employed in the clinical workflow of 1-view treatments to get patient-related information for customized margin definition., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: At introduction in 2014, dose calculation for the first MLC on a robotic SRS/SBRT platform was limited to a correction-based Finite-Size Pencil Beam (FSPB) algorithm. We report on the dosimetric accuracy of a novel Monte Carlo (MC) dose calculation algorithm for this MLC, included in the Precision™ treatment planning system., Methods: A phantom was built of one slab (5.0 cm) of lung-equivalent material (0.09…0.29 g/cc) enclosed by 3.5 cm (above) and 5 cm (below) slabs of solid water (1.045 g/cc). This was irradiated using rectangular (15.4 × 15.4 mm 2 to 53.8 × 53.7 mm 2 ) and two irregular MLC-fields. Radiochromic film (EBT3) was positioned perpendicular to the slabs and parallel to the beam. Calculated dose distributions were compared to film measurements using line scans and 2D gamma analysis., Results: Measured and MC calculated percent depth dose curves showed a characteristic dose drop within the low-density region, which was not correctly reproduced by FSPB. Superior average gamma pass rates (2%/1 mm) were found for MC (91.2 ± 1.5%) compared to FSPB (55.4 ± 2.7%). However, MC calculations exhibited localized anomalies at mass density transitions around 0.15 g/cc, which were traced to a simplification in electron transport. Absence of these anomalies was confirmed in a modified build of the MC engine, which increased gamma pass rates to 96.6 ± 1.2%., Conclusions: The novel MC algorithm greatly improves dosimetric accuracy in heterogeneous tissue, potentially expanding the clinical use of robotic radiosurgery with MLC. In-depth, independent validation is paramount to identify and reduce the residual uncertainties in any software solution., (Copyright © 2018. Published by Elsevier Ltd.)

The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. This particular TQC contains detailed performance objectives and safety criteria for CyberKnife ® Technology. The quality control recommendations in this document are based upon previously published guidelines and the collective experience of all Canadian sites using this technology. This TQC guideline has been field tested at the newest Canadian CyberKnife installation site and includes recommendations for quality control of the Iris™ and InCise™ MLC collimation systems., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany., Methods/design: This German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3-5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients., Discussion: The HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials., Study Status: The study is ongoing and currently recruiting patients., Trial Registration: Registration number: NCT02635256 ( clinicaltrials.gov ). Registered 8 December 2015.

Background: As irradiated brain volume at 12 Gy (V12) is a predictor for radionecrosis, the purpose of the study was to develop a model for Cyberknife (CK) plans that is able to predict the lowest achievable V12 at a given tumor size and prescription dose (PD), and to suggest a new quality index regarding V12 for optimizing the treatment planning of brain metastases., Method: In our model V12 was approximated as a spherical shell around the tumor volume. The radial distance between tumor surface and the 12 Gy isodose line was calculated using an approximation of the mean dose gradient in that area. Assuming a radially symmetrical irradiation from the upper half space, the dose distribution is given by the superposition of single fields. The dose profiles of a single field were derived by the measured off-center ratios (OCR) of the CK system. Using the calculated gradients of the sum dose profiles, minimal-V12 was estimated for different tumor sizes. The model calculation was tested using a phantom dataset and retrospectively applied on clinical cases., Results: Our model allows the prediction of a best-case scenario for V12 at a given tumor size and PD which was confirmed by the results of the isocentric phantom plans. The results of the non-isocentric phantom plans showed that an optimization of coverage caused an increase in V12. This was in accordance with the results of the retrospective analysis. V12 s of the clinical cases were on average twice that of the predicted model calculation. A good agreement was achieved for plans with an optimal conformity index (nCI). Re-planning of cases with high V12 showed that lower values could be reached by selecting smaller collimators and by allowing a larger number of total MU and more MU per beam., Conclusions: V12 is a main parameter for assessing plan quality in terms of radiotoxicity. The index f12 defined as the ratio of V12 from the actual plan with the evaluated V12 from our model describes the conformity of an optimally possible V12 and thus can be used as a new quality index for optimizing treatment plans.

Purpose: Robotic radiosurgery requires plan delivery quality assurance (DQA) but there has never been a published comprehensive analysis of a patient-specific DQA process in a clinic. We proposed to evaluate 350 consecutive film-based patient-specific DQAs using statistical process control. We evaluated the performance of the process to propose achievable tolerance criteria for DQA validation and we sought to identify suboptimal DQA using control charts., Methods and Material: DQAs were performed on a CyberKnife-M6 using Gafchromic-EBT3 films. The signal-to-dose conversion was performed using a multichannel-correction and a scanning protocol that combined measurement and calibration in a single scan. The DQA analysis comprised a gamma-index analysis at 3%/1.5mm and a separate evaluation of spatial and dosimetric accuracy of the plan delivery. Each parameter was plotted on a control chart and control limits were calculated. A capability index (Cpm) was calculated to evaluate the ability of the process to produce results within specifications., Results: The analysis of capability showed that a gamma pass rate of 85% at 3%/1.5mm was highly achievable as acceptance criteria for DQA validation using a film-based protocol (Cpm>1.33). 3.4% of DQA were outside a control limit of 88% for gamma pass-rate. The analysis of the out-of-control DQA helped identify a dosimetric error in our institute for a specific treatment type., Conclusion: We have defined initial tolerance criteria for DQA validations. We have shown that the implementation of a film-based patient-specific DQA protocol with the use of control charts is an effective method to improve patient treatment safety on CyberKnife., (Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Stereotactic radiation technique including single fraction radiosurgery and conventional fractionated stereotactic radiotherapy is widely reported as an effective treatment of pituitary adenomas. Because of the restricted radiation tolerance dose of the optic pathway, single fraction radiosurgery has been accepted for small tumor located far away from the optic apparatus, while fractionated stereotactic radiotherapy may be suitable for larger tumor located close to the optic pathway. More recently, hypofractionated stereotactic radiotherapy has become an alternative treatment option that provides high rate of tumor control and visual preservation for the perioptic lesions within 2 to 3 mm of the optic pathway. The objective of the study was to analyze the clinical outcomes of perioptic pituitary adenomas treated with hypofractionated stereotactic radiotherapy. From 2009 to 2012, 40 patients with perioptic pituitary adenoma were treated with CyberKnife robotic radiosurgery. The median tumor volume was 3.35 cm 3 (range, 0.82-25.86 cm 3 ). The median prescribed dose was 25 Gy (range, 20-28 Gy) in 5 fractions (range, 3-5). After the median follow-up time of 38.5 months (range, 14-71 months), 1 (2.5%) patient with prolactinoma had tumor enlargement, 31 (77.5%) were stable, and the remaining 8 (20%) tumors were smaller in size. No patient's vision deteriorated after hypofractionated stereotactic radiotherapy. Hormone normalization was observed in 7 (54%) of 13 patients. No newly developed hypopituitarism was detected in our study. These data confirmed that hypofractionated stereotactic radiotherapy achieved high rates of tumor control and visual preservation. Because of the shorter duration of treatment, it may be preferable to use hypofractionated stereotactic radiotherapy over fractionated stereotactic radiotherapy for selected pituitary adenomas immediately adjacent to the optic apparatus., (© The Author(s) 2015.)

The purpose of this study was to evaluate the role of diffusion-weighted MR imaging (DW-MRI) in the assessment of treatment response of primary or secondary liver malignancies after stereotactic radiosurgery (SRS) using robotic radiosurgery. All patients who underwent SRS therapy for hepatic malignancies who had pre- and post-interventional MR examinations including DW-MRI at our hospital between 02/2010 and 02/2012 were included. A retrospective analysis of the institutional imaging database identified 13 patients (4 men, 9 women, mean age: 66 years) with a total of 14 primary or secondary liver malignancies. Criteria of tumor response to treatment were a decrease in size and/or loss of contrast enhancement as assessed with respect to RECIST criteria. Mean apparent diffusion coefficient (ADC) values for normal liver parenchyma and hepatic masses in each MR examination were calculated and compared using two-tailed, paired t-test with a significance level of 0.05. Mean ADC values of liver malignancies were 1.10 ± 0.30 x 10(-3) mm(2)/s, 1.48 ± 0.35 x 10(-3) mm(2)/s and 1.56 ± 0.40 x 10(-3) mm(2)/s on pre-interventional, the first post-interventional, and the second post-interventional DW-MRI. There was a significant increase of ADC values between the pre-interventional examination and the first and second post-interventional follow-up exams (p < 0.01 and p = 0.01, respectively). However, there was no statistical difference between the ADC values of the first and second post-interventional MRI. ADC values of normal liver parenchyma did not show significant changes in ADC values during pre- and post-interventional MRI. ADC measurements may allow the evaluation of response to treatment of hepatic malignancies by SRS. ADC values of liver malignancies increase significantly after SRS treatment., (© The Author(s) 2014.)

Stereotactic body radiation therapy (SBRT) to central lung tumors is associated with normal -tissue toxicity. Highly conformal technologies may reduce the risk of complications. This study compares physical dose characteristics and anticipated risks of radiation pneumonitis (RP) among three SBRT modalities: robotic radiosurgery (RR), helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT). Nine patients with central lung tumors ≤5 cm were compared. RR, HT and VMAT plans were developed per RTOG 0831. Dosimetric comparisons included target coverage, conformity index, heterogeneity index, gradient index, maximal dose at 2 cm from target (D2 cm), and dose-volume parameters for organs at risk (OARs). Efficiency endpoints included total beam-on time and monitor units. RP risk was derived from Lyman-Kutcher-Burman modeling on in-house software. The average GTV and PTV were 11.6 ± 7.86 cm(3) and 36.8 ± 18.1 cm(3). All techniques resulted in similar target coverage (p = 0.64) and dose conformity (p = 0.88). While RR had sharper fall-off gradient (p = 0.002) and lower D2 cm (p = 0.02), HT and VMAT produced greater homogeneity (p < 0.001) and delivery efficiency (p = 0.001). RP risk predicted from whole or contralateral lung volumes was less than 10%, but was 2-3 times higher using ipsilateral volumes. Using whole (p = 0.04, p = 0.02) or ipsilateral (p = 0.004, p = 0.0008) volumes, RR and VMAT had a lower risk of RP than HT. Using contralateral volumes, RR had the lowest RP risk (p = 0.0002, p = 0.0003 versus HT, VMAT). RR, HT and VMAT were able to provide clinically acceptable plans following the guidelines provided by RTOG 0813. All techniques provided similar coverage and conformity. RR seemed to produce a lower RP risk for a scenario of small PTV-OAR overlap and small PTV. VMAT and HT produced greater homogeneity, potentially desirable for a large PTV-OAR overlap. VMAT probably yields the lowest RP risk for a large PTV. Understanding subtle differences among these technologies may assist in situations where multiple choices of modality are available., (© The Author(s) 2014.)

Background: Prospective analysis of oligo-brain metastasis in Indian patients treated with SRS-only treatment. Methods: Between January 2017 and May 2022, 235 patients were screened and 138 histologically proven and radiologically confirmed. One to five brain metastasis patients aged more than 18 years with good Karnofsky performance status (KPS >70) accrued in ethical and scientific committee-approved prospective observational study protocol for treatment with only radiosurgery (SRS) with robotic radiosurgery (CyberKnife, CK) [AIMS IRB: 2020-071; CTRI No: REF/2022/01/050237]. Immobilization was performed with a thermoplastic mask, contrast CT simulation was performed with 0.625 mm slices, fused with T1 contrast/T2 FLAIR MRI images for contouring. Planning target volume (PTV) margin of 2–3 mm and a dose of 20–30 Gy in 1–5 fractions. Response to treatment, new brain lesions free survival, overall survival, and toxicity profile after CK were evaluated. Results: In total, 138 patients with 251 lesions were accrued (median age 59 years (interquartile range [IQR] 49–67 years; female 51%; headache in 34%, motor deficit in 7%, KPS >90 in 56%; lung primary in 44%, breast in 30%; oligo-recurrence in 45%; synchronous oligo-metastases in 33%; adenocarcinoma primary in 83%). One hundred seven patients (77%) received upfront Stereotactic radiotherapy (SRS), 15 (11%) received postoperative SRS, 12 (9%) received whole brain radiotherapy (WBRT) before SRS, and 3 (2%) received WBRT plus SRS boost. The majority had solitary (56%) brain metastasis, 28% had two to three lesions, and 16% had four to five brain lesions. Frontal (39%) was the most common site. Median PTV was 15.5 mL (IQR – 8.1–28.5 mL). Seventy-one (52%) patients were treated with single fractions, 14% with three, and 33% with five fractions. Fraction schedules were 20–2 4 Gy/1fr; 27 Gy/3fr, and 25 Gy/5 fractions (mean BED 74.6 Gy [SD ± 48.1; mean MU 16608], mean treatment time was 49 min (range 17–118 min]. Twelve Gy normal brain volume was 40.8 mL (3.2%) (range 19.3–73.7 mL). At a mean follow-up of 15 months (SD 11.9 months; max 56 months), the mean actuarial OS after SRS-only treatment was 23.7 months (95% confidence interval [CI] 20–28). Further 124 (90%) patients had >3 months, 108 (78%) had >6 months, 65 (47%) had >12 months, and 26 (19%) had >24 months follow-up. Intracranial disease and extracranial disease were controlled in 72 (52.2%) and 60 (43.5%), respectively. "In-field" recurrence, "out-of-field," and "both in and out-of-field" recurrences were in 11%, 42%, and 46%, respectively. At the last follow-up, 55 patients (40%) were alive, 75 (54%) died due to disease progression, and the status of 8 (6%) patients was not known. Among 75 patients who died, 46 (61%) had extracranial disease progression, 12 (16%) had only intracranial progression, and 8 (11%) had unrelated causes. Also, 12/117 (9%) had radiological confirmation of radiation necrosis. Prognostication based on western patients (primary tumor type, number of lesions extracranial disease) showed similar outcomes. Conclusions: SRS alone in brain metastasis is feasible in the Indian subcontinent with similar survival outcomes, recurrence patterns, and toxicity as published in the western literature. Patient selection, dose schedule, and planning need to be standardized to have similar outcomes. WBRT can be safely omitted in Indian patients with oligo-brain metastasis. Western prognostication nomogram is applicable in the Indian patient population. [ABSTRACT FROM AUTHOR]

Introduction: Following the resection of brain metastases (BM), whole-brain radiotherapy (WBRT) is a long-established standard of care. Its position was recently challenged by the less toxic single-session radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) of the resection cavity, reducing dose exposure of the healthy brain. Patients and Methods: We analyzed 101 patients treated with either SRS/FSRT (n = 50) or WBRT (n = 51) following BM resection over a 5-year period. Propensity score adjustment was done for age, total number of BM, timepoint of BM diagnosis, controlled primary and extracranial metastases. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS), local control (LC) and distant brain control (DBC). Results: Median patient age was 61 (interquartile range, IQR: 56–67) years and the most common histology was non-small cell lung cancer, followed by breast cancer. 38% of the patients had additional unresected BM. Twenty-four patients received SRS, 26 patients received FSRT and 51 patients received WBRT. Median OS in the SRS/FSRT subgroup was not reached (IQR NA−16.7 months) vs. 12.6 months (IQR 21.3–4.4) in the WBRT subgroup (hazard ratio, HR 3.3, 95%-CI: [1.5; 7.2] p < 0.002). Twelve-months LC-probability was 94.9% (95%-CI: [88.3; 100.0]) in the SRS subgroup vs. 81.7% (95%-CI: [66.6; 100.0]) in the WBRT subgroup (HR 0.2, 95%-CI: [0.01; 0.9] p = 0.037). Twelve-months DBC-probabilities were 65.0% (95%-CI: [50.8; 83.0]) and 58.8% (95%-CI: [42.9; 80.7]), respectively (HR 1.4, 95%-CI: [0.7; 2.7] p = 0.401). In propensity score-adjusted multivariate analysis, incomplete resection negatively impacted OS (HR 3.9, 95%-CI: [2.0;7.4], p < 0.001) and LC (HR 5.4, 95%-CI: [1.3; 21.9], p = 0.018). Excellent clinical performance (HR 0.4, 95%-CI: [0.2; 0.9], p = 0.030) and better graded prognostic assessment (GPA) score (HR 0.4, 95%-CI: [0.2; 1.0], p = 0.040) were prognostic of superior OS. A higher number of BM was associated with a greater risk of developing new distant BM (HR 5.6, 95%-CI: [1.0; 30.4], p = 0.048). In subgroup analysis, larger cavity volume (HR 1.1, 95%-CI: [1.0; 1.3], p = 0.033) and incomplete resection (HR 12.0, 95%-CI: [1.2; 118.3], p = 0.033) were associated with inferior LC following SRS/FSRT. Conclusion: This is the first propensity score-adjusted direct comparison of SRS/FSRT and WBRT following the resection of BM. Patients receiving SRS/FSRT showed longer OS and LC compared to WBRT. Future analyses will address the optimal choice of safety margin, dose and fractionation for postoperative stereotactic RT of the resection cavity. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic radiosurgery (SRS) is becoming more frequently used for patients with multiple brain metastases (BMs). Single-isocenter volumetric modulated arc therapy (SI-VMAT) is an emerging alternative to dedicated systems such as CyberKnife (CK). We present a dosimetric comparison between CyberKnife M6 and SI-VMAT, planned at RayStation V8B, for the simultaneous SRS of five or more BM. Patients and Methods: Twenty treatment plans of CK-based single-session SRS to ≥5 brain metastases were replanned using SI-VMAT for delivery at an Elekta VersaHD linear accelerator. Prescription dose was 20 or 18 Gy, conformally enclosing at least 98% of the total planning target volume (PTV), with PTV margin-width adapted to the respective SRS technique. Comparatively analyzed quality metrics included dose distribution to the healthy brain (HB), including different isodose volumes, conformity, and gradient indices. Estimated treatment time was also compared. Results: Median HB isodose volumes for 3, 5, 8, 10, and 12 Gy were consistently smaller for CK-SRS compared to SI-VMAT (p < 0.001). Dose falloff outside the target volume, as expressed by the gradient indices GI_high and GI_low, was consistently steeper for CK-SRS compared to SI-VMAT (p < 0.001). CK-SRS achieved a median GI_high of 3.1 [interquartile range (IQR), 2.9–1.3] vs. 5.0 (IQR 4.3–5.5) for SI-VMAT (p < 0.001). For GI_low, the results were 3.0 (IQR, 2.9–3.1) for CK-SRS vs. 5.6 (IQR, 4.3–5.5) for SI-VMAT (p < 0.001). The median conformity index (CI) was 1.2 (IQR, 1.1–1.2) for CK-SRS vs. 1.5 (IQR, 1.4–1.7) for SI-VMAT (p < 0.001). Estimated treatment time was shorter for SI-VMAT, yielding a median of 13.7 min (IQR, 13.5–14.0) compared to 130 min (IQR, 114.5–154.5) for CK-SRS (p < 0.001). Conclusion: SI-VMAT offers enhanced treatment efficiency in cases with multiple BM, as compared to CyberKnife, but requires compromise regarding conformity and integral dose to the healthy brain. Additionally, delivery at a conventional linear accelerator (linac) may require a larger PTV margin to account for delivery and setup errors. Further evaluations are warranted to determine whether the detected dosimetric differences are clinically relevant. SI-VMAT could be a reasonable alternative to a dedicated radiosurgery system for selected patients with multiple BM. [ABSTRACT FROM AUTHOR]

Aim This study evaluates the toxicity and outcome in patients treated with robotic radiosurgery for liver metastases. Background Modern technologies allow the delivery of high doses to the liver metastases while lowering the dose to the neighboring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known yet. Methods and materials A total of 9 patients with 17 liver metastases have been treated with robotic stereotactic body radiotherapy SBRT from March 2011 to December 2014. Local response to SBRT was graded by the Response Evaluation Criteria in Solid Tumors criteria to describe change in treated tumor lesion. Adverse events after SBRT were graded on a 1–5 scale according to the National Cancer Institute common terminology criteria for adverse events v4.0. Results Patients received either three (78%) or five (22%) fractions. Patients were treated with a mean fraction dose of 14 Gy with a range from 9 to 20 Gy. The median total radiation dose provided to patients was 45 Gy with a range of 45–60 Gy. Four out of the 17 (23.5%) treated lesions had a complete response, 9 (53%) partial response and 3 (17.6%) stable disease. With a median follow-up of 15.2 months after SBRT treatment, local control and overall survival rated were 89% and 66%, respectively. No patient experienced grade ≥3 toxicity. The most common toxicity reported was asthenia. Only two patients had nausea and diarrhea, 10 and 14 days after SBRT, respectively. Conclusions Robotic radiosurgery is a safe and effective local treatment option for secondary liver tumors. Further prospective studies are ongoing to determine long-term response and survival after robotic-SBRT for liver metastases. [ABSTRACT FROM AUTHOR]

Purpose: The "InCise™multileaf-collimator (MLC)" is the first commercial MLC to be mounted on a robotic SRS/SBRT platform (CyberKnife). The authors assessed characteristics and performance of this novel device in a preclinical five months test period. Methods: Commissioning beam data were acquired with unshielded diodes. EBT3 radiochromic films were employed for measurement of transmission, leaf/bank position accuracy (garden fence) before and after exercising the MLC, for end-to-end testing and further characterization of the beam. The robot workspace with MLC was assessed analytically by transformation to an Euler geometry ("plane," "gantry," and "collimator" angles) and by measuring pointing accuracy at each node. Stability over time was evaluated in picket fence and adapted Winston-Lutz tests (AQA). Results: Beam penumbrae (80%-20%, with 100% = 2×dose at inflection point for field sizes ≥ 50 ×50 mm2) were 2.2-3.7 mm for square fields in reference condition (source-axis-distance 800 mm, depth 15 mm) and depended on field size and off-axis position. Transmission and leakage did not exceed 0.5%. Accessible clinical workspace with MLC covered non-coplanar gantry angles of [-113°; +112°] and collimator angles of [-100°; +107°], with an average robot pointing accuracy of 0.12±0.09 mm. For vertical beams, garden fence tests exhibited an average leaf positioning error of ≤0.2 mm, which increased by 0.25 and 0.30 mm (banks X1 and X2) with leaves traveling parallel to gravity. After execution of a leaf motion stress routine, garden fence tests showed slightly increased jaggedness and allowed to identify one malfunctioning leaf motor. Total system accuracy with MLC was 0.38±0.05 mm in nine end-to-end tests. Picket fence and AQA tests displayed stable results over the test period. Conclusions: The InCise™ MLC for CyberKnife showed high accuracy and adequate characteristics for SRS/SBRT applications. MLC performance after exercise demands specific quality assurance measures. [ABSTRACT FROM AUTHOR]

The AAPM TG-135 report is a landmark recommendation for the quality assurance (QA) of image-guided robotic radiosurgery. The purpose of this paper is to present results pertaining to intentionally offsetting the phantom as recommended by TG-135 and to present data on targeting algorithm accuracy as a function of imager parameters in less than ideal circumstances, which had not been available at the time of publication of TG-135. Methods: All tests in this study were performed at the Cooper University Hospital CyberKnife Center in Mt. Laurel, NJ. For intentional offsets, initial tests were performed on the Accuray-supplied anthropomorphic head and neck phantom, whereas for subsequent tests, the Accuray-supplied alignment quality assurance (AQA) phantom was used. To simulate the effects of imager parameters for larger patients, slabs of Blue Water (Standard Imaging, Inc., Middleton, WI) were added to attenuate the x-ray images in some of the tests. In conjunction with attenuated x-ray tests, the number of fiducials was varied by systematically deselecting them one at a time at the CyberKnife console. Results: Tests using the AQA phantom verified that submillimeter alignments were consistently achieved even with intentional shifts and rotations of up to 10.0 mm and 1.0°, respectively. An analysis of 17 months of daily QA alignment tests showed that submillimeter alignments were achieved more than 99% of the time even with such intentional shifts and rotations of the phantom. When additional slabs of Blue Water were added to simulate patient attenuation of the x-ray images, targeting errors could be induced depending on imager parameters and the amount of Blue Water used. A series of consecutive tests showed that two helpful variables to ensure good accuracy of the system were (1) the fiducial extraction confidence level (FECL) system parameter and (2) the number of targeted fiducials. When fewer than four fiducials were used, the FECL reported by the CyberKnife was sometimes high even when a false lock occurred, so using multiple fiducials helped to ensure reliable targeting. Conclusions: Radiosurgery requires the highest degree of targeting accuracy, and in our experience, the CyberKnife has been able to maintain submillimeter accuracy consistently. It has been verified that our CyberKnife can correct for phantom shifts of up to 10.0 mm and rotations of up to 1.0°. It has also been discovered that false locks are more likely to occur with a single fiducial than with multiple fiducials. Although targeting accuracy can only be measured on a phantom, the insight gained from analyzing the QA tests can help us in devising better strategies for achieving the best treatment for our patients. [ABSTRACT FROM AUTHOR]

Purpose: To compare volumetric modulated arc therapy of RapidArc with robotic stereotactic body radiation therapy (SBRT) of CyberKnife in the planning and delivery of SBRT for hepatocellular carcinoma (HCC) treatment by analyzing dosimetric parameters. Materials and Methods: Two radiation treatment plans were generated for 29 HCC patients, one using Eclipse for the RapidArc plan and the other using Multiplan for the CyberKnife plan. The prescription dose was 60 Gy in 3 fractions. The dosimetric parameters of planning target volume (PTV) coverage and normal tissue sparing in the RapidArc and the CyberKnife plans were analyzed. Results: The conformity index was 1.05 ± 0.02 for the CyberKnife plan, and 1.13 ± 0.10 for the RapidArc plan. The homogeneity index was 1.23 ± 0.01 for the CyberKnife plan, and 1.10 ± 0.03 for the RapidArc plan. For the normal liver, there were significant differences between the two plans in the low-dose regions of V1 and V3. The normalized volumes of V60 for the normal liver in the RapidArc plan were drastically increased when the mean dose of the PTVs in RapidArc plan is equivalent to the mean dose of the PTVs in the CyberKnife plan. Conclusion: CyberKnife plans show greater dose conformity, especially in small-sized tumors, while RapidArc plans show good dosimetric distribution of low dose sparing in the normal liver and body. [ABSTRACT FROM AUTHOR]

Aim of the study: The purpose of this study was to evaluate the efficacy and safety of applying CyberKnife (CK) radiosurgery in patients with spinal metastases. Material and methods: Twenty-eight patients with vertebral metastases treated using the CK system were included in the study. Eleven patients suffered from pain, and in 1 case neurological symptoms were observed. The remaining patients were free from clinical symptoms of metastatic disease. The doses applied ranged between 8 and 40 Gy delivered in 4 fractions of 8-15 Gy. Results: In the first follow-up evaluation (mean 4.5 months after the treatment), pain was stable in 5 of 8 evaluable cases and in 3 regression occurred. The last follow-up examination (mean 11 months after stereotactic radiosurgery) revealed stable ailments in 3 of 6 evaluable cases, improvement in 3 and new complaints in another 4 patients. In 17 patients imaging studies were conducted after a mean time of 11 months after CK treatment. Stabilization was confirmed in 11, regression in 4 and progression in 2 cases. Median overall survival was 20.6 months. Median progression-free survival was 12.6 months. No side effects attributable to the treatment were observed, but during follow-up transient or permanent deterioration in neurological status as a consequence of disease progression was diagnosed in 4 patients. Delivery time of a single fraction ranged between 0.5 and 1.5 hours. Conclusions: Robotic stereotactic radiosurgery as part of multimodality therapy for metastatic spinal tumours is safe and effective. Because of long irradiation times, this kind of treatment is not suitable for patients in poor general condition. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the technique, dosimetry, dose-volume-histograms (DVHs) and acute toxicity for CyberKnife® boost irradiation instead of intra-cervical brachytherapy in patients with cervical cancer. Methods and materials: Eleven who were not suitable for brachytherapy with FIGO stage IIB-IIIB cervical cancer underwent primary chemoradiation. After fiducial implantation, T2 contrast-enhanced planning MRI and CT scans at 2-mm slice thickness were collected in the treatment position. The clinical target volume was defined as cervix + macroscopic residual tumour on MRI. Five fractions of 6 Gy each were prescribed to the target volume with a covering single dose 6 Gy. DVH parameters were evaluated for the target and organs at risk. Acute toxicity was documented once a week. Results: DmeanPTV ranged from 33.6-40 Gy, median 36.7 Gy with a coverage of the PTV calculated to 100% of the prescribed dose ranging from 93.0-99.3% (median 97.7%). For the PTV the median CN was 0.78 (range, 0.66 to 0.87) and the median CI was 1.28 (range 1.15 to 1.52). Gastrointestinal (GI) and genitourinary (GU) toxicity was mild. There was no grade 3 or higher GI and GU toxicity. After 6 months of follow up, there were no local recurrences. For the complete treatment, a median EQD2 to 1 cc and 2 cc of the bladder wall was 98.8 Gy and 87.1 Gy, respectively. Median EQD2 to 1 cc and 2 cc of the rectal wall was 72.3 Gy and 64 Gy, respectively, correlating with a risk < 10% for Grade 2-4 late toxicity. Conclusions: CyberKnife robotic radiosurgery in patients with cervical cancer provides excellent target coverage with steep dose gradients toward normal tissues and safe DVH parameters for bladder, rectum and sigmoid. Acute toxicity was mild. Longer follow-up is needed to evaluate the oncological equality. [ABSTRACT FROM AUTHOR]

Background Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods A total of 50 patients with recurrent gynecologic cancer who had single or multiple (⩽4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to control for prognostic variables. Findings SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%) and diarrhea (4%). One (2%) grade 4 hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 (68% [95% CI, 53.2, 80.1]) patients. No SBRT-targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5). Interpretation SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway. Funding Case Comprehensive Cancer Center. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the clinical accuracy of the respiratory motion tracking system of the CyberKnife treatment device. Methods and Materials: Data in log files of 44 lung cancer patients treated with tumor tracking were analyzed. Errors in the correlation model, which relates the internal target motion with the external breathing motion, were quantified. The correlation model error was compared with the geometric error obtained when no respiratory tracking was used. Errors in the prediction method were calculated by subtracting the predicted position from the actual measured position after 192.5 ms (the time lag to prediction in our current system). The prediction error was also measured for a time lag of 115 ms and a new prediction method. Results: The mean correlation model errors were less than 0.3 mm. Standard deviations describing intrafraction variations around the whole-fraction mean error were 0.2 to 1.9 mm for cranio–caudal, 0.1 to 1.9 mm for left–right, and 0.2 to 2.5 mm for anterior–posterior directions. Without the use of respiratory tracking, these variations would have been 0.2 to 8.1 mm, 0.2 to 5.5 mm, and 0.2 to 4.4 mm. The overall mean prediction error was small (0.0 ± 0.0 mm) for all directions. The intrafraction standard deviation ranged from 0.0 to 2.9 mm for a time delay of 192.5 ms but was halved by using the new prediction method. Conclusions: Analyses of the log files of real clinical cases have shown that the geometric error caused by respiratory motion is substantially reduced by the application of respiratory motion tracking. [Copyright &y& Elsevier]

Simple Summary: Radiotherapy plays a vital role in the multimodal treatment of pediatric central nervous system (CNS) tumors. In cases of small-to-medium-sized, well-demarcated lesions, high-precision treatment modalities such as stereotactic radiosurgery (SRS) are well-established in adult patients. SRS and, more specifically, robotic radiosurgery (RRS) and robotic stereotactic radiotherapy (RSRT) have only limited evidence in the field of pediatric neuro-oncology. This systematic review aims to report and assess the available RRS and RSRT data and studies. Results demonstrate that both treatment modalities are infrequently applied and primarily used in specific situations, including postoperative, palliative, and salvage treatments. Treatment outcomes are encouraging, but high-quality studies are lacking. Prospective studies are necessary to determine the actual utility of RRS and RSRT in pediatric neuro-oncology. Nevertheless, RRS and RSRT may be applied for selected patients. Background: CyberKnife-based robotic radiosurgery (RRS) is a widely used treatment modality for various benign and malignant tumors of the central nervous system (CNS) in adults due to its high precision, favorable safety profile, and efficacy. Although RRS is emerging in pediatric neuro-oncology, scientific evidence for treatment indications, treatment parameters, and patient outcomes is scarce. This systematic review summarizes the current experience and evidence for RRS and robotic stereotactic radiotherapy (RSRT) in pediatric neuro-oncology. Methods: We performed a systematic review based on the databases Ovid Medline, Embase, Cochrane Library, and PubMed to identify studies and published articles reporting on RRS and RSRT treatments in pediatric neuro-oncology. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied herein. Articles were included if they described the application of RRS and RSRT in pediatric neuro-oncological patients. The quality of the articles was assessed based on their evidence level and their risk for bias using the original as well as an adapted version of the Newcastle Ottawa Quality Assessment Scale (NOS). Only articles published until 1 August 2021, were included. Results: A total of 23 articles were included after final review and removal of duplicates. Articles reported on a broad variety of CNS entities with various treatment indications. A majority of publications lacked substantial sample sizes and a prospective study design. Several reports included adult patients, thereby limiting the possibility of data extraction and analysis of pediatric patients. RRS and RSRT were mostly used in the setting of adjuvant, palliative, and salvage treatments with decent local control rates and acceptable short-to-intermediate-term toxicity. However, follow-up durations were limited. The evidence level was IV for all studies; the NOS score ranged between four and six, while the overall risk of bias was moderate to low. Conclusion: Publications on RRS and RSRT and their application in pediatric neuro-oncology are rare and lack high-quality evidence with respect to entity-related treatment standards and long-term outcomes. The limited data suggest that RRS and RSRT could be efficient treatment modalities, especially for children who are unsuitable for surgical interventions, suffer from tumor recurrences, or require palliative treatments. Nevertheless, the potential short-term and long-term adverse events must be kept in mind when choosing such a treatment. Prospective studies are necessary to determine the actual utility of RRS and RSRT in pediatric neuro-oncology. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with metastatic renal cell carcinoma are difficult to treat despite many new systemic therapy options. Patients often present with pulmonary metastases. Local treatment of those metastases is traditionally performed surgically. In this study, robotic radiosurgery is tested in 50 patients with pulmonary metastases and is demonstrated to be a safe and highly effective treatment option in this patient group. Future research might focus on the combination of robotic radiosurgery with systemic treatment. Pulmonary metastases are the most frequent site of metastases in renal cell carcinoma (RCC). Metastases directed treatment remains an important treatment option despite advances in systemic therapies. However, the safety and efficacy of robotic radiosurgery (RRS) for the treatment of lung metastases of RCC remains unclear. Patients with metastatic RCC and lung metastases treated by RRS were retrospectively analyzed for overall survival (OS), progression-free survival (PFS), local recurrence free survival (LRFS) and adverse events. The Kaplan–Meier method was used for survival analysis and the common terminology criteria for adverse events (CTCAE; Version 5.0) classification for assessment of adverse events. A total of 50 patients were included in this study. Median age was 64 (range 45–92) years at the time of RRS. Prior to RRS, 20 patients (40.0%) had received either tyrosine kinase inhibitors or immunotherapy and 27 patients (54.0%) were treatment naïve. In our patient cohort, the median PFS was 13 months (range: 2–93). LRFS was 96.7% after two years with only one patient revealing progressive disease of the treated metastases 13 months after RRS. Median OS was 35 months (range 2–94). Adverse events were documented in six patients (12%) and were limited to grade 2. Fatigue (n = 4) and pneumonitis (n = 2) were observed within 3 months after RRS. In conclusion, RRS is safe and effective for patients with metastatic RCC and pulmonary metastases. Radiation induced pneumonitis is specific in the treatment of pulmonary lesions, but not clinically relevant and survival rates seem favorable in this highly selected patient cohort. Future directions are the implementation of RRS in multimodal treatment approaches for oligometastatic or oligoprogressive disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Meningiomas represent the most common central nervous system (CNS) tumor. Despite their often benign nature, a tumor location in direct proximity to vital brain structures may lead to significant morbidity. This is the case for foramen magnum meningiomas (FMMs) as they grow at the skull base, next to the brain stem and foramen magnum. Surgical resection represents the mainstay of FMM treatments. In patients unsuitable for surgery, with tumor recurrences or tumor remnants after surgery, non-invasive treatment modalities may play a crucial role in patient management. Reports and studies on stereotactic radiosurgery (SRS) for the treatment of FMMs are scarce. This multicenter analysis reported the outcome data of 62 patients with FMMs. SRS achieved a high local tumor control and demonstrated a favorable safety profile. These results are in agreement with previous findings. SRS should be considered for selected FMM patients. Background: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. Methods: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. Results: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. Conclusions: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery. [ABSTRACT FROM AUTHOR]

The development of the CyberKnife technology, a combination of image guidance and industrial robotics, led to a paradigm shift in radiosurgery. The CyberKnife Robotic Radiosurgery System consists of a 6-MV compact LINAC mounted on a computer-controlled robotic manipulator capable of 6 degrees of freedom, with a dedicated image-guidance system which acquires X-ray images during treatment. Apart from standard neurosurgical indications (i.e., acoustic neurinomas, meningiomas, brain metastases, etc.) radiosurgical applications are currently evolving to include extracranial indications such as tumors of the spine, pancreas, lung, and liver. We reviewed the indications and outcomes in the first 1,000 patients treated in the CyberKnife Center Munich. Single-dose treatment was chosen because published clinical studies have demonstrated high efficacy and low morbidity for intracranial and spinal tumors. A recent development in radiosurgery is breathing-triggered real-time correction for respiratory motion of tumors, which makes it possible to apply radiosurgical doses to moving targets. CyberKnife treatment is designed to be delivered on an outpatient basis, mostly consisting of a single treatment session lasting between 60 and 90 min. High quality imaging is of utmost importance for successful radiosurgical applications. For example, high-field MRI, multislice CT’s, PET and PET-CT imaging data must be integrated in the planning phase for optimal target definition. A total of 750 patients with brain tumors were treated at the CyberKnife Center Munich in cooperation with the Department of Neurosurgery of the University Munich. A total of 285 patients with brain metastases received 339 treatments for 780 brain metastases. The first 55 spinal tumor patients were analyzed and have a mean follow-up of 14 months (out of 200 spinal tumor patients treated at our facility). Efficacy was high and complications minimal for all patient groups. CyberKnife radiosurgery technology may be used as a primary treatment modality or in multidisciplinary cancer therapy. Patient selection, high quality diagnostic imaging and consideration of alternative modes of therapy are key issues in optimizing the benefits of CyberKnife treatment. [ABSTRACT FROM AUTHOR]