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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]

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]

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]

Purpose To quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT). Methods and Materials Twenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections. Results The proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections. Conclusions Accurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an effective surrogate to tumor motion, fiducials provide a close estimation of both rigid and nonrigid motion of liver tumors. The reported displacements could be further utilized for tumor margin definition and motion management in conventional linear accelerator-based liver SBRT. [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.