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Purpose: To design a patient specific quality assurance (PSQA) process for the CyberKnife Synchrony system and quantify its dosimetric accuracy using a motion platform driven by patient tumor traces with rotation. Methods: The CyberKnife Synchrony system was evaluated using a motion platform (MODUSQA) and a SRS MapCHECK phantom. The platform was programed to move in the superior‐inferior (SI) direction based on tumor traces. The detector array housed by the StereoPhan was placed on the platform. Extra rotational angles in pitch (head down, 4.0° ± 0.15° or 1.2° ± 0.1°) were added to the moving phantom to examine robot capability of angle correction during delivery. A total of 15 Synchrony patients were performed SBRT PSQA on the moving phantom. All the results were benchmarked by the PSQA results based on static phantom. Results: For smaller pitch angles, the mean gamma passing rates were 99.75% ± 0.87%, 98.63% ± 2.05%, and 93.11% ± 5.52%, for 3%/1 mm, 2%/1 mm, and 1%/1 mm, respectively. Large discrepancy in the passing rates was observed for different pitch angles due to limited angle correction by the robot. For larger pitch angles, the corresponding mean passing rates were dropped to 93.00% ± 10.91%, 88.05% ± 14.93%, and 80.38% ± 17.40%. When comparing with the static phantom, no significant statistic difference was observed for smaller pitch angles (p = 0.1 for 3%/1 mm), whereas a larger statistic difference was observed for larger pitch angles (p < 0.02 for all criteria). All the gamma passing rates were improved, if applying shift and rotation correction. Conclusions: The significance of this work is that it is the first study to benchmark PSQA for the CyberKnife Synchrony system using realistically moving phantoms with rotation. With reasonable delivery time, we found it may be feasible to perform PSQA for Synchrony patients with a realistic breathing pattern. [ABSTRACT FROM AUTHOR]

Objectives To evaluate patient-specific quality assurance (PSQA) of 3 targets in a single delivery using a novel film-based phantom. Methods The phantom was designed to rotate freely as a sphere and could measure 3 targets with film in a single delivery. After identifying the coordinates of 3 targets in the skull, the rotation angles about the equator and meridian were computed for optimal phantom setup, ensuring the film plane intersected the 3 targets. The plans were delivered on the CyberKnife system using fiducial tracking. The irradiated films were scanned and processed. All films were analysed using 3 gamma criteria. Results Fifteen CyberKnife test plans with 3 different modalities were delivered on the phantom. Both automatic and marker-based registration methods were applied when registering the irradiated film and dose plane. Gamma analysis was performed using a 3%/1 mm, 2%/1 mm, and 1%/1 mm criteria with a 10% threshold. For the automatic registration method, the passing rates were 98.2% ± 1.9%, 94.2% ± 3.7%, and 80.9% ± 6.3%, respectively. For the marker-based registration approach, the passing rates were 96.4% ± 2.7%, 91.7% ± 4.3%, and 78.4% ± 6.2%, respectively. Conclusions A novel spherical phantom was evaluated for the CyberKnife system and achieved acceptable PSQA passing rates using TG218 recommendations. The phantom can measure true-composite dose and offers high-resolution results for PSQA, making it a valuable device for robotic radiosurgery. Advances in knowledge This is the first study on PSQA of 3 targets concurrently on the CyberKnife system. [ABSTRACT FROM AUTHOR]

Objective: To determine the long-term normal tissue complication probability with stereotactic body radiation therapy (SBRT) treatments for targets that move with respiration and its relation with the type of respiratory motion management (tracking vs. compression or gating). Methods: A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator. Results: Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range. Conclusion: Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature. [ABSTRACT FROM AUTHOR]

Purpose There is no consensus on the optimal prescription isodose line ( IDL) in CyberKnife ( CK) SRS. We designed a strategy to search for optimal CK plans at different levels of IDLs and investigated the dosimetric impact on the quality of CK plans. Methods and materials The retrospective study consisted of 13 CK patients with 16 brain tumors. The mean volume and size of the tumors was 9.7 ± 10.4 cc and 30.3 ± 10.9 mm, respectively. Four shells were created at distances of 2-3 mm to 60 mm from the target. The constraint dose of the innermost shell (D1) was the primary optimization parameter. For isolated brain tumors, D1 started from the prescription dose and gradually reduced after optimization started over. The optimal plans were reached when the coverage started to degrade and the desired IDL was achieved. For eight tumors abutting an OAR, both the D1 and constraint dose to the OAR were gradually pushed until an optimal plan was reached for the desired IDL. Results For the isolated tumors, the V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V25 Gy of low IDL (49.6 ± 2.1%) plans were on average 23.6%, 28.6%, 33.8%, 26.2%, and 10.6% lower, respectively, comparing to the high IDL (88.6 ± 1.3%) plans. The Conformality Index ( CI) of the low IDL plans outperformed the high IDL plans (mean: 1.15 vs. 1.24), except for a lesion under 0.5 cc. The quality of the middle IDL plans (69.6 ± 1.5%) was close to the low IDL plans. Similar results were observed for tumors abutting an OAR. Conclusions Low IDL plans outperformed high IDL plans for all metrics in tumors > 0.5 cc. The lower dose exposure of normal brain tissue and better CI could potentially reduce radiation necrosis while the higher maximum dose could improve local control. [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: Treatment option of stereotactic radiosurgery versus whole brain radiotherapy for multiple brain metastases (>10) is an ongoing debate. Detailed dosimetric and biological information are presented in this study to investigate the possible clinical outcomes. Materials and Methods: Nine patients with multiple brain metastases (11-25) underwent stereotactic radiosurgery. Whole brain radiotherapy plans are retrospectively designed with the same MR image set and the same structure set for each patient using the standard opposing lateral beams and fractionation (3 Gy × 10). Physical doses and biologically effective doses are calculated for each lesion target and the CNS normal tissues and they are compared between whole brain radiotherapy and stereotactic radiosurgery in the context of clinical efficacy and published toxicities. Results: Tumor biologically effective dose is higher in radiosurgery than in whole brain radiotherapy by factors of 3.2-5.3 in maximum dose and of 2.4-3.1 in mean dose. Biologically effective mean dose in radiosurgery is 1.3-34.3% for normal brain, 0.7-31.6% for brainstem, 0.5-5.7% for chiasm, 0.2-5.7% for optic nerves and 0.6-18.1% for hippocampus of that in whole brain radiotherapy over nine cases presented here. We also presented the dose-volume relationship for normal brain to address the dosimetric concerns in radiosurgery. Conclusions: Dose-volume metrics presented in this study are essential to understanding the safety and efficacy of whole brain radiotherapy and/or radiosurgery for multiple brain metastases. Whole brain radiotherapy has resulted in higher incidence of radiation-related toxicities than radiosurgery. Even for patients with more than 10 brain metastases, the CNS normal tissues receive significantly lower doses in radiosurgery. Mean normal brain dose in SRS is found to correlate with the total volume of lesions rather than the number of lesions treated. [ABSTRACT FROM AUTHOR]

Introduction. Brachytherapy plays a key role in the treatment of many gynecologic cancers. However, some patients are unable to tolerate brachytherapy for medical or other reasons. For these patients, stereotactic body radiotherapy (SBRT) offers an alternative form of treatment. Methods. Retrospective review of patients prospectively collected on SBRT database is conducted. A total of 11 gynecologic patients who could not have brachytherapy received SBRT for treatment of their malignancies. Five patients have been candidates for interstitial brachytherapy, and six have required tandem and ovoid brachytherapy. Median SBRT dose was 25 Gy in five fractions. Results. At last followup, eight patients were alive, and three patients had died of progressive disease. One patient had a local recurrence. Median followup for surviving patients was 420 days (median followup for all patients was 120 days). Two patients had acute toxicity (G2 dysuria and G2 GI), and one patient had late toxicity (G3 GI, rectal bleeding requiring cauterization). Conclusions. Our data show acceptable toxicity and outcome for gynecologic patients treated with SBRT who were unable to receive a brachytherapy boost. This treatment modality should be further evaluated in a phase II study. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the dosimetric feasibility of accelerated partial breast irradiation (APBI) using CyberKnife. Methods: Fourteen previously treated patients with early-stage breast cancer were selected for a retrospective study. Six of these patients had been treated to 38.5 Gy in 10 fractions in a phase III accelerated partial breast trial and the rest of the patients were treated to 50.4 Gy in 28 fractions. In this planning study, the guidelines in the protocol for the phase III partial breast trial were followed for organ delineation and CyberKnife planning. The achievable dosimetric parameters from all CyberKnife plans were compared to Intensity-modulated radiation therapy (IMRT) and 3D-CRT methods. The reproducibility of the dose delivery with and without respiratory motion was assessed through delivering a patient plan to a breast phantom. Different dose calculation algorithms were also compared between ray tracing and Monte Carlo. Results: For all the patients in the study, the dosimetric parameters met the guidelines from the NSABP B39/RTOG 0413 protocol strictly. The mean PTV volume covered by 100% of the prescription dose was 95.7 ± 0.7% (94.7%-97.1%). The mean maximal dose was 104 ± 2% of the prescription dose. The mean V50% and mean V100% to the ipsilateral normal breast were 23.1 ± 11.6% and 9.0 ± 5.8%, respectively. The conformity index of all plans was 1.14 ± 0.04. The maximum dose to the contralateral breast varied from 1.3 cGy to 111 cGy. The mean V5% and mean V30% to the contralateral and ipsilateral lungs were 1.0 ± 1.6% and 1.3 ± 1.2%, respectively. In our study, the mean V5% to the heart was 0.2 ± 0.5% for right-sided tumors and 9.4 ± 10.1% for left-sided tumors. Compared with IMRT and 3D-CRT planning, the PTV coverage from CyberKnife planning was the highest, and the ratio of V20% to V100% of the breast from CyberKnife planning was the smallest. The heart and lung doses were similar in all the techniques except that the V5% for the lung and heart in CyberKnife planning was slightly higher. Conclusions: The dosimetric feasibility of APBI using CyberKnife was investigated in this retrospective study. All the dosimetric parameters strictly met the guidelines from the NSABP B39/RTOG 0413 protocol. With advanced real-time tracking capability, CyberKnife should provide better target coverage and spare nearby critical organs for APBI treatment. [ABSTRACT FROM AUTHOR]

PURPOSE AND OBJECTIVES: To estimate effects of tumor growth factor inhibitors on stereotactic body radiation therapy (SBRT) dose tolerance, we reviewed the literature and our patient experience. METHODS: Review of the literature revealed the Barney et al dataset (Int J Radiat Oncol Biol Phys. 2013;87:73–80), which provided SBRT small bowel dose-volume histogram (DVH) data for D5cc, D2cc, Dmax, and other volumes, as well as the corresponding outcomes. Combining their data with ours yielded 175 small bowel contours, 54 managed with inhibitors of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), or mammalian target of rapamycin (mTOR) before or after SBRT, from May 2008 through December 2014. No patient in either institution received VEGF, EGFR, or mTOR inhibitors concurrently with SBRT; for our patients, we maintain a 2-week period between SBRT and biologic agents. All doses were first converted to three-fraction equivalent dose using the linear quadratic (LQ) model with alpha/beta = 3 Gy. DVH data were loaded into the DVH Evaluator software (DiversiLabs LLC, Huntingdon Valley, PA), which produced a probit dose-response model to estimate the risk level for each published dose tolerance limit. RESULTS: Seven Common Terminology Criteria for Adverse Events version 4 grade 3–5 gastrointestinal toxicities were associated with VEGF in the published dataset. The probit dose-response model of 175 data points was used to estimate the risk level. In three fractions, the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the the Clinic) Dmax ≤ 30 Gy limit had a 7% risk, and the TG101 Dmax ≤ 25.2 Gy limit had a 3.6% risk. A simple ratio approximated the increased risk from the inhibitors, as 7 of 54 cases with inhibitors and 7 of 175 overall cases had complications; therefore, the increased risk is approximately (7 of 54)/(7 of 175), for a 3.2-fold greater risk. However, none of the patients from our institution who were managed with VEGF, EGFR, or mTOR inhibitors had grade ≥ 3 complications. CONCLUSION: Tumor growth factor inhibitors may cause more toxicity with SBRT than would otherwise be anticipated, although the absence of complications in our patients allows cautious optimism. [ABSTRACT FROM AUTHOR]

PURPOSE: Major blood vessel toxicity data from stereotactic body radiation therapy (SBRT) are particularly sparse. Therefore, we investigated aorta and major vessel dose-response models to determine tolerance in patients treated with 1 to 5 fractions. METHODOLOGY: A total of 625 major vessel structures, including aorta, vena cava, pulmonary artery, and pulmonary vein, were analyzed via dose-volume histograms (DVHs). From July 2008 to February 2015, a total of 387 cases with major vessels exposed to 1 to 5 fractions of SBRT with CyberKnife (Accuray, Inc., Palo Alto, CA) in our institution were studied. These data were combined with DVH data on 238 major vessels from the 2014 Nishimura study (J Thorac Oncol 2014;9:1370–6). The median number of fractions was 5, so the linear quadratic model with alpha/beta = 3 Gy was used to convert all doses to 5-fraction equivalent doses prior to any other modeling. DVH Evaluator software (DiversiLabs, LLC, Huntingdon Valley, PA) was utilized to create a logistic dose-response model of the aggregate dataset using maximum likelihood parameter fitting. RESULTS: The published dataset included three Common Terminology Criteria for Adverse Events version 4 grade 3–5 pulmonary artery complications, and there were no observable major vessel complications in our dataset. The logistic model TD50 for Dmax was 81 Gy, and the slope parameter was 3.13. Models for V25Gy, D4cc, D1cc, and D0.5cc will also be presented. When the 73 pulmonary artery contours from Nishimura (2014) were analyzed alone, the risk was increased by approximately fivefold, but it is not known whether this was due to intrinsically increased sensitivity or attributable to lack of data in the omission of 552 noncomplication data points. CONCLUSIONS: From logistic modeling of 625 major vessels, the Radiation Therapy Oncology Group 0813 trial limit of Dmax = 52.5 Gy in five fractions was found to have a 1.2% risk of grade 3–5 toxicity, and the 2008 Timmerman limit of Dmax = 45 Gy in three fractions had a 2.3% risk. Further investigation is warranted, especially for the pulmonary artery, which might not have a dose tolerance as high as other major vessels. [ABSTRACT FROM AUTHOR]

Introduction. Brachytherapy plays a key role in the treatment of many gynecologic cancers. However, some patients are unable to tolerate brachytherapy for medical or other reasons. For these patients, stereotactic body radiotherapy (SBRT) offers an alternative form of treatment. Methods. Retrospective review of patients prospectively collected on SBRT database is conducted. A total of 11 gynecologic patients who could not have brachytherapy received SBRT for treatment of their malignancies. Five patients have been candidates for interstitial brachytherapy, and six have required tandem and ovoid brachytherapy. Median SBRT dose was 25 Gy in five fractions. Results. At last followup, eight patients were alive, and three patients had died of progressive disease. One patient had a local recurrence. Median followup for surviving patients was 420 days (median followup for all patients was 120 days). Two patients had acute toxicity (G2 dysuria and G2 GI), and one patient had late toxicity (G3 GI, rectal bleeding requiring cauterization). Conclusions. Our data show acceptable toxicity and outcome for gynecologic patients treated with SBRT who were unable to receive a brachytherapy boost. This treatment modality should be further evaluated in a phase II study. [ABSTRACT FROM AUTHOR]