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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., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Intrinsic DNA properties including bending play a crucial role in diverse biological systems. A recent advance in a high-throughput technology called loop-seq makes it possible to determine the bendability of hundred thousand 50-bp DNA duplexes in one experiment. However, it's still challenging to assess base-resolution sequence bendability in large genomes such as human, which requires thousands of such experiments. Here, we introduce 'BendNet'-a deep neural network to predict the intrinsic DNA bending at base-resolution by using loop-seq results in yeast as training data. BendNet can predict the DNA bendability of any given sequence from different species with high accuracy. To explore the utility of BendNet, we applied it to the human genome and observed DNA bendability is associated with chromatin features and disease risk regions involving transcription/enhancer regulation, DNA replication, transcription factor binding and extrachromosomal circular DNA generation. These findings expand our understanding on DNA mechanics and its association with transcription regulation in mammals. Lastly, we built a comprehensive resource of genomic DNA bendability profiles for 307 species by applying BendNet, and provided an online tool to assess the bendability of user-specified DNA sequences (http://www.dnabendnet.com/)., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: Treatment of small cell lung cancer (SCLC) with brain metastatic disease has traditionally involved whole brain radiation therapy (WBRT). The role of stereotactic radiosurgery (SRS) is unclear., Methods and Materials: Our study was a retrospective review of an SRS database evaluating patients with SCLC who received SRS. A total of 70 patients and 337 treated brain metastases (BM) were analyzed. Forty-five patients had previous WBRT. The median number of treated BM was 4 (range, 1-29)., Results: Median survival was 4.9 months (range, 0.70-23.9). The number of treated BM was correlated with survival; patients with fewer BM had improved overall survival ( P < .021). The number of treated BM was associated with different brain failure rates; 1-year central nervous system control rates were 39.2% for 1 to 2 BM, 27.6% for 3 to 5 BM, and 0% for >5 treated BM. Patients with previous WBRT had worse brain failure rates ( P < .040). For patients without previous WBRT, the 1-year distant brain failure rate was 48%, and median time to distant failure was 15.3 months., Conclusions: SRS for SCLC in patients with <5 BM appears to offer acceptable control rates. Patients with >5 BM have high rates of subsequent brain failure and are not ideal candidates for SRS., Competing Interests: 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., (© 2023 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

The purpose of the study was to introduce and evaluate a high-resolution diode array for patient-specific quality assurance (PSQA) of CyberKnife brain stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). Thirty-three intracranial plans were retrospectively delivered on the SRS MapCHECK using fixed cone, Iris, and multileaf collimator (MLC). The plans were selected to cover a range of sites from large tumor bed, single/multiple small brain metastases (METs) to trigeminal neuralgia. Fiducial tracking using the four fiducials embedded around the detector plane was used as image guidance. Results were analyzed before and after registration based on absolute dose gamma criterion of 1 mm distance-to-agreement and 0.5%-3% dose-difference. Overall, the gamma passing rates (1 mm and 3% criterion) before registration for all the patients were above 90% for all three treatment modalities (96.8 ± 3.5%, the lowest passing rate of 90.4%), and were improved after registration (99.3 ± 1.5%). When tighter criteria (1 mm and 2%) were applied, the gamma passing rates after registration for all the cases dropped to 97.3 ± 3.2%. For trigeminal neuralgia cases, we applied 1 mm and 0.5% criterion and the passing rates dropped from 100 ± 0.0% to 98.5 ± 2.0%. The mean delivery time was 33.4 ± 11.7 min, 24.0 ± 4.9 min, and 17.1 ± 2.6 min for the fixed cone, Iris, and MLC, respectively. With superior gamma passing rates and reasonable quality assurance (QA) time, we believe the SRS MapCHECK could be a good option for routine PSQA for CyberKnife SRS/SRT., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

The relationship between serum spermidine levels and future cardiovascular disease risk has not yet been well elucidated in the general population based on community studies. Using a nested case-control study, we estimated the association between serum spermidine level and future stroke. New stroke cases had higher baseline levels of spermidine than controls [182.8 (141.8-231.5) vs. 152.0 (124.3-193.0), P < 0.001]. After multivariable adjustment, individuals with spermidine ≥ 205.9 nmol/L (T3) higher risks of stroke (HR 5.02, 95% CI 1.58-16.02) with the lowest quartile (< 136.9 nmol/L) as reference. The association between serum spermidine levels and risk of stroke seemed to be consistent and was reproducible in our cross-sectional studies. In addition, comparisons of the areas under receiver operator characteristics curves confirmed that a model including spermidine had better discrimination than without (0.755 vs. 0.715, P = 0.04). Here we report a close relationship exists between serum spermidine levels and risk of stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Xie, Sun, Zhang, Ma, Xu, Zheng, Xu, Li, Guo, Sun, Xing, Sun and Wen.)

Background: Spermidine, a natural polyamine, was found critically involved in cardioprotection and lifespan extension from both animal experiments and human studies., Aims: This study aimed to evaluate the effect of serum spermidine levels on the prognosis in patients with acute myocardial infarction (AMI) and investigate the potential mediation effect of oxidative stress in the above relationship., Methods: We included 377 patients with AMI in a prospective cohort study and measured serum spermidine and oxidative stress indexes (superoxide dismutase enzymes, glutathione peroxidase, and Malondialdehyde) using high-performance liquid chromatography with fluorescence detector and enzyme-linked immunosorbent assay, respectively. The associations of spermidine with AMI outcomes were evaluated using Cox proportional hazards models., Results: 84 (22.3%) major adverse cardiac events (MACE) were documented during a mean follow-up of 12.3 ± 4.2 months. After multivariable adjustment, participants with serum spermidine levels of ≥15.38 ng/mL (T3) and 7.59-5.38 ng/mL (T2) had hazard ratio (HR) for recurrent AMI of 0.450 [95% confidence interval (CI): 0.213-0.984] and 0.441 (95% CI: 0.215-0.907) compared with the ≤7.59 ng/mL (T1), respectively. Participants in T3 and T2 had HR for MACE of 0.566 (95% CI: 0.329-0.947) and 0.516 (95% CI: 0.298-0.893) compared with T1. A faint J-shaped association was observed between serum spermidine levels and the risk of MACE ( p -nonlinearity = 0.036). Comparisons of areas under receiver operator characteristics curves confirmed that a model including serum spermidine levels had greater predictive power than the one without it (0.733 versus 0.701, p = 0.041). A marginal statistically significant mediation effect of superoxide dismutase was shown on the association between spermidine and MACE ( p = 0.091)., Conclusions: Serum spermidine was associated with an improved prognosis in individuals with AMI, whereas the underlying mechanism mediated by oxidative stress was not found.

Purpose: This is a single arm phase 2 study (Clinical trials.gov NCT02568033) to examine the role of stereotactic body radiotherapy (SBRT) along with full dose systemic chemotherapy in the treatment of unresectable stage 2 and stage 3 nonsmall cell lung cancer. Primary endpoints are disease free survival and toxicity., Materials: Patients were treated with SBRT to all sites of gross disease. Dosing consisted of 60 Gy in 3 fractions for peripheral lung tumors, 50 Gy in 5 fractions for central lung tumors, and 40 to 50 Gy in 5 fractions for hilar and mediastinal lymph nodes. Chemotherapy consisted of 4 cycles of pemetrexed and cisplatin or carboplatin and paclitaxel for nonsquamous histology and cisplatin and docetaxel or cisplatin and paclitaxel for squamous histology. SBRT was given in between the chemotherapy cycles. There was a 7 days break between chemotherapy and SBRT. Quality of life was measured using functional assessment of cancer therapy-lung., Results: Twenty two patients were enrolled and analyzed. Seventeen (77%) were stage III and 19 (86%) had lymph node involvement. Median follow-up for all patients was 23.1 months. Median overall survival is 27.2 months. Overall survival at 1 year was 82% and overall survival at 2 years was 53%. Median disease free survival is 16.0 months with a 2-year regional failure rate of 19% and 2-year distant failure rate of 47.2%. There were 6 grade 3 acute toxicities and 2 late grade 3 or higher toxicities including 1 grade 5 hemoptysis. Quality of life scores were unchanged compared with baseline., Conclusion: A combination of SBRT and full dose chemotherapy appears to be a safe and effective treatment for locally advanced NSCLC and warrants further investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Preoperative radiation followed by surgical resection is a standard treatment for soft-tissue sarcomas (STS). We report on 2 consecutive, phase 2, single-arm studies evaluating 5 fraction stereotactic body radiation therapy (SBRT) treatments followed by surgical resection for STS (clinical trails.gov NCT02706171)., Methods and Materials: A total of 16 patients were treated with preoperative SBRT. Tumor size in the greatest dimension was a median 6.7 cm (maximum: 14 cm) and the majority of STS were in the extremities. SBRT consisted of 35 to 40 Gy in 5 fractions every other day., Results: Median follow-up time was 1719 days (4.7 years). Grade ≥3 acute toxicity occurred in 1 patient (grade 3 skin changes). Fifteen patients proceeded with surgical resection. Three patients had a wound complication after surgery, 1 patient had grade ≥3 late toxicity (grade 4 requiring surgical intervention). There was 1 local recurrence and 5 distant recurrences., Conclusions: Long-term follow-up on SBRT for STS found acceptable control and toxicity rates, and warrants further evaluation., (© 2021 The Authors.)

The impact of selection of prescription isodose line (IDL) on plan quality has not been well evaluated during inverse planning (IP). In this study, a total of 180 IP plans at five levels of IDL were generated for 30 brain metastases (BMs). For each BM, one round of IP was performed with typical IP settings, followed by a quick fine-tuning to ensure the same target coverage and comparable conformality index. The impact of the IDL on the quality metrics (selectivity, gradient index [GI], and treatment time) was evaluated. The decrease of selectivity and increase of GI meant inferior target dose conformality and more dose spillage. Additionally, a metric directly correlated to the treatment time was proposed. For all cases, the mean GI decreased monotonically as IDL decreased from 70% to 30%, and the decreasing rate was significantly different based on tumor size. The mean selectivity and number of shots decreased monotonically as IDL decreased for all the tumors. From 70% to 30% IDL, the decreasing rate of the mean selectivity was 2.8% (p = 0.020), 7.7% (p = 0.005), and 15.4% (p = 0.020) and that of the number of shots was 75.4% (p = 0.001), 73.2% (p = 0.001), and 50.7% (p = 0.009), for the large, medium, and small tumors, respectively. For the medium and small tumor groups, the mean treatment time increased monotonically when IDLs decreased (increasing rate was 80.0% [p = 0.002] for medium tumors [p = 0.001] and 130.8% [p = 0.001] for small tumors from 70% to 30%). For the large tumors, the mean treatment time was the shortest at 50% IDL (59.0 min) and higher at 70% (65.9 min) and 30% (71.9 min). Overall, the GammaPlan chose smaller sectors for plans with lower IDLs except for the large size group., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The purpose of our study was to explore the association of blood pressure (BP) changes on short-and long-term outcomes of major adverse cardiovascular events (MACEs) in rural China. This study was designed to learn the effects of BP changes (2004-2008) on short-term (2008-2010, within 2 years of the initial examination) and long-term (2008-2017) outcomes of MACE, including 24 285 and 27 290 participants, respectively. In this study, 423 (short-term) and 1952 (long-term) MACEs were identified. For prehypertension to hypertension, the risk of long-term stroke was increased (hazard ratio [HR] = 1.18 [1.00-1.39]). For hypertension to prehypertension, the short-term MACE risk (0.65 [0.47-0.90]), short-term stroke risk (0.45 [0.26-0.76]), and long-term stroke risk (0.83 [0.70-0.99]) all decreased. Short-term outcomes conferred a stronger impact than long-term outcomes (Fisher Z test, measured as the difference of β coefficients, all P < .05).

Plant symptoms are derived from specific interactions between virus and host components. However, little is known about viral or host factors that participate in the establishment of systemic necrosis. Here, we showed that helper component proteinase (HCPro), encoded by Chilli veinal mottle virus (ChiVMV), could directly interact with catalase 1 (CAT1) and catalase 3 (CAT3) in the cytoplasm of tobacco (Nicotiana tabacum) plants to facilitate viral infection. In vitro, the activities of CAT1 and CAT3 were inhibited by the interaction between HCPro and CATs. The C-terminus of HCPro was essential for their interaction and was also required for the decrease of enzyme activities. Interestingly, the mRNA and protein level of CATs were up-regulated in tobacco plants in response to ChiVMV infection. Nicotiana tabacum plants with HCPro overexpression or CAT1 knockout were more susceptible to ChiVMV infection, which was similar to the case of H2O2-pre-treated plants, and the overexpression of CAT1 inhibited ChiVMV accumulation. Also, neither CAT1 nor CAT3 could affect the RNA silencing suppression (RSS) activity of HCPro. Our results showed that the interaction between HCPro and CATs promoted the development of plant systemic necrosis, revealing a novel role for HCPro in virus infection and pathogenicity., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Purpose We proposed a planning strategy that utilized tuning targets to guide GammaKnife (GK) Inverse Planning (IP) to deliver higher dose to the tumor, while keeping acceptable dose to the abutting organ at risk (OAR). Methods Ten patients with a large portion of brain tumor abutting the OAR previously treated with GK stereotactic radiosurgery (SRS) were selected. For each patient, multiple tuning targets were created by cropping the target contour from three-dimensional (3D) expansions of the OAR. The number of the tuning targets depended on the complexity of the planning process. To demonstrate dose sparing effect, an IP plan was generated for each tuning target after one round of optimization without shot fine-tuning. In the dose enhancement study, a more aggressive target dose was prescribed to the tuning target with a larger margin and one to two shots were filled in the region with missing dose. The resulting plans were compared to the previously approved clinical plans. Results For all 10 patients, a dose sparing effect was observed, i.e. both target coverage and dose to the OARs decreased when the margins of 3D expansion increased. For one patient, a margin of 6 mm was needed to decrease the maximum dose to the optical chiasm and optical nerve by 44.3% and 28.4%, respectively. For the other nine patients, the mean dropping rate of V12Gyto brain stem were 28.2% and 59.5% for tuning targets of 1 and 2 mm margins, respectively. In the dose enhancement study, the tuning-target-guided plans were hotter than the approved treatment plans, while keeping similar dose to the OARs. The mean of the treatment and enhancement dose was 15.6 ± 2.2 Gy and 18.5 ± 3.2 Gy, respectively. The mean coverage of the target by prescription dose was slightly higher in the enhancement plans (96.9 ± 2.6% vs 96.3 ± 3.6%), whereas the mean coverage of the enhancement dose was 20.1% higher in the enhancement plans (89.6 ± 9.0% vs 74.6 ± 19.9%). Conclusions We demonstrated that an inverse planning strategy could facilitate target dose enhancement for challenging GK cases while keeping acceptable OAR dose., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Xu et al.)

The Leksell GammaPlan (LGP) with an inverse planning (IP) tool has been upgraded to version 11.1 since its launch in 2010. We evaluated its IP planning performance by re-planning 16 targets that had been planned using forward planning (FP). The FP and IP plans were compared. A planning guideline for IP process was developed aiming for an unbiased comparison. Sixteen brain metastases (BMs) without nearby critical structures were included in the study (size > 1 cm for all targets). All prior FP were re-planned in the LGP using IP and maintaining the same beam-on time and coverage. The dose to all the targets was scaled to 20 Gy in a single fraction at 50% isodose line (IDL) for FP and IP comparison purpose. The coverage and beam-on time were nearly the same for both the FP and IP plans. For all the IP plans, the mean selectivity was 0.85 ± 0.04 (vs 0.83 ± 0.04 in FP plans, p = 0.02), the mean GI was 2.92 ± 0.21 (vs 3.18 ± 0.60 in FP plans, p = 0.047), the mean V12Gy was 8.18 ± 8.57 cc (vs 9.09 ± 9.08 cc in FP plans, p = 0.001), the mean V8Gy was 14.63 ± 15.14 cc (vs 16.34 ± 16.17 cc in FP plans, p = 0.001), and the mean V5Gy was 29.01 ± 28.77 cc (vs 32.77 ± 31.41 cc in FP plans, p = 0.001). The number of shots was higher in IP plans (means of 16.69 ± 8.11 vs 10.81 ± 6.87 in FP plans, p = 0.001). We retrospectively re-planned 16 FP plans using the IP tool while meeting the quality limiting factors for the FP plans. The dosimetry parameters from the IP plans outperformed the treated FP plans and the IP tool should be preferred for tumors with size > 1 cm., (Copyright © 2020 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose In the current Gamma Knife (GK) planning system (GammaPlan, version 10.2, Elekta AB, Stockholm, Sweden), multiple adjacent brain metastasis (BMs) had to be planned sequentially if BMs were drawn separately, leading to less conformal target dose in the composite plan due to inter-target dose contribution and fine-tuning of the shots being quite tedious. We proposed a method to improve target dose conformality and planning efficiency for such cases. Methods and Materials Fifteen patients with multiple BMs treated on the Leksell GK Perfexion system were retrospectively replanned in the Institutional Review Board (IRB) approved study. The recruitment criterion was all the BMs should be entirely encompassed within the maximum dose grid allowed in the GammaPlan. The BMs were first planned sequentially as routine clinic cases. The contours of the BMs were then exported to the VelocityAI (Varian, CA, USA) to generate a composite contour after a union operation, and all the BMs were planned again simultaneously using this composite contour in the GammaPlan. The inverse planning (IP) was employed in both methods with the same treatment time allowed for a fair plan comparison. Dose evaluation was performed in the VelocityAI with all planning magnetic resonance (MR) images, structure set and dose were exported to the VelocityAI. The dosimetery parameters, including conformality index (CI), V20Gy, V16Gy, V12Gy, and V5Gy, were compared between the two methods. Results The planning results from both methods were reviewed qualitatively and quantitatively. The proposed method exhibited superior CI, except for an outlier case with very tiny BMs. The mean and standard deviation (std.) of the Paddick CI for all patients were 0.76±0.11 for the proposed method, comparing to 0.69±0.13 for the sequential method. The V20Gy, V16Gy, V12Gy, and V5Gy for the proposed method were 10.9±0.9%, 9.5±10.2%, 6.2±16.4% and 3.3±21.8%, all lower than those from the sequential method. Conclusions The proposed method showed improved target dose conformality for all cases except for very tiny BMs. Planning efficiency is considerably better with the combined target technique. The improved dose conformality will be beneficial to patients in long term with lowered risk of radiation necrosis after GK stereotactic radiosurgery (SRS)., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Locally recurrent, previously irradiated primary head and neck tumors have historically been associated with poor outcomes. Stereotactic body radiation therapy has emerged as a feasible and promising treatment option for tumor recurrence, particularly in nonsurgical candidates. This study aimed to assess the associated outcomes of stereotactic body radiation therapy used in this setting., Methods: Retrospective analysis of a prospectively collected database of 25 patients treated with CyberKnife for unresectable, recurrent head and neck cancer in a previously irradiated field. The primary end points evaluated were rates of survival, tumor control, and treatment-related toxicities., Results: Median survival of the study population was 7.5 months (range, 1.5-47.0 months). Median survival of the 20 (80%) patients who were treated with curative purpose was 8.3 months. One-year overall survival rate for the entire population was 32%. The respective 1-year and 2-year survival rates for the curative subcohort were 40% and 20%, respectively. Local and locoregional failure occurred in 8 (32%) and 7 (28%) patients, respectively. Low severe acute (4%) and late (6%) treatment-related toxicity rates were observed. No grade 4 or 5 toxicities were observed., Conclusion: Stereotactic body radiation therapy is a viable treatment option for patients with unresectable, recurrent head and neck cancer. Significant tumor control rates are achievable with minimal severe toxicity. Although perhaps associated with patient selection and a heterogeneous sample, overall survival of stereotactic body radiation therapy outcomes appears unfavorable.

Objectives: Preoperative radiation followed by surgical resection is a standard treatment for soft tissue sarcomas (STSs). The conventional method of radiation is 5 weeks to approximately 50 Gy. We report on our initial experience and phase II single-arm study assessing 5 fractions of stereotactic body radiotherapy (SBRT), followed by surgical resection for STS., Methods: Thirteen patients and 14 tumors were treated with preoperative SBRT; tumors were mostly poorly differentiated (5) or myxoid (5) and were located on the leg (10), arm (2) or groin (2). The median tumor size in greatest dimension was 7.6 cm (maximum 16 cm). Twelve patients received 35 Gy in 5 fractions; for 2 deeper tumors the dose was 40 Gy in 5 fractions. Ten patients were administered 0.5 cm bolus to improve the dose. Gross tumor volume was expanded 0.5 cm radially and 3 cm along the tissue plane. Treatment was to an isodose line (median 81%) and was delivered every other day. Maximum dose to the skin was 46 Gy (median 41 Gy)., Results: The median follow-up period was 279 days. Surgical resection occurred a median of 37 days after completion of SBRT. Four patients had acute toxicity consisting of 2 grade 2 and 2 grade 3 skin reactions; all cases of skin toxicity resolved by the time of surgery. Percent tumor necrosis ranged from 10% to 95% (median 60%). All patients had negative margins. Planned vacuum-assisted wound closure was used in 4 patients; there were no other major wound complications. There was 1 local recurrence and 7 distant recurrences., Conclusion: This is the initial experience of radiosurgery for preoperative treatment of STSs. We have found this to be well tolerated, convenient for the patients, and a much shorter treatment course, allowing patients to undergo surgery and subsequent chemotherapy quicker. Surgical complications and control rates are satisfactory. The initial results are encouraging for further investigation.

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., (© 2017 American Association of Physicists in Medicine.)

Background: Stereotactic body radiotherapy (SBRT) is a well-established treatment option for early stage non-small-cell lung cancer (NSCLC) tumors < 5 cm. There is limited information on tumors > 5 cm., Patients and Methods: We performed retrospective data collection of patients enrolled onto a prospective SBRT registry study. Eligible patients for this study had node-negative NSCLC measuring > 5 cm in any dimension. Data from 41 patients were analyzed. Median patient age was 75 years, and median tumor size was 5.6 cm (range, 5.0-12.2 cm). Sixteen patients had squamous disease, 20 patients adenocarcinoma, and 1 mixed tumor; 4 patients had no biopsy. Median radiation dose per fraction was 50 Gy in 5 fractions. Radiation was prescribed to isodose line, median 66% (range, 50%-84%)., Results: Before SBRT, 6 patients had previous chemotherapy and 7 patients had previous radiation. Median follow-up for all patients was 15.2 months (range, 0.56-48.1 months). At last follow-up, 16 patients were still alive, with a median follow-up of 16.1 months for surviving patients. The median survival was 17.5 months with 1- and 2-year survivals of 65% and 34%. Two patients (4.8%) had local failure, and 13 patients (31%) had distant failure. Four patients (9.8%) had acute toxicity, and 7 patients (17.1%) had late toxicity, including 2 (4.8%) grade 3 late toxicities., Conclusion: SBRT for tumors > 5 cm is effective, with good local control rates and acceptable toxicity. The main pattern of failure is distant, suggesting a possible role for systemic chemotherapy in these patients., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate a plastic scintillation detector for the measurement of small field dosimetry and to verify the accuracy of measured dose in comparison with Monte Carlo calculation in a heterogeneous medium., Methods: The study is performed with CyberKnife planning and delivery system. The setup consists of a custom made solid lung phantom with the insert of an Exradin W1 scintillation detector or an Exradin A16 ion chamber. The measurement was done for a series of cone sizes from 5 mm to 60 mm, and the dose was calculated by Monte Carlo algorithm in MultiPlan workstation. The difference between measurement and calculation was reported., Results: Our preliminary results demonstrated the applicability of plastic scintillation detectors in the measurement of small field dosimetry in a heterogeneous medium. The difference between the calculated and measured output factors was less than 3% for all cone sizes from 60 mm down to 5 mm. Without any corrections, the measured dose from the scintillation detector calibrated to the ion chamber reading was also within 3% of the Monte Carlo calculation in the lung phantom for cone sizes 20 mm or larger., Conclusions: Small field dosimetry is particularly relevant to stereotactic radiation treatment. The accuracy of dose calculation for small static beams is critical to dose planning so would potentially affect the treatment outcomes in a heterogeneous medium. Our results have shown good agreement with plastic scintillation detector in both homogeneous and heterogeneous medium., (© 2017 American Association of Physicists in Medicine.)

Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we organized these diverse published limits with MD Anderson at Cooper data into a unified framework, constructing the dose-volume histogram (DVH) Risk Map, demonstrating low-risk and high-risk SBRT dose tolerance limits for small bowel. Statistical models of clinical data from 2 institutions were used to assess the safety spectrum of doses used in the exposure of the gastrointestinal tract in SBRT; 30% of the analyzed cases had vascular endothelial growth factor inhibitors (VEGFI) or other biological agents within 2 years before or after SBRT. For every dose tolerance limit in the DVH Risk Map, the probit dose-response model was used to estimate the risk level from our clinical data. Using the current literature, 21Gy to 5cc of small bowel in 3 fractions has low toxicity and is reasonably safe, with 6.5% estimated risk of grade 3 or higher complications, per Common Terminology Criteria for Adverse Events version 4.0. In the same fractionation for the same volume, if lower risk is required, 16.2Gy has an estimated risk of only 2.5%. Other volumes and fractionations are also reviewed; for all analyzed high-risk small bowel limits, the risk is 8.2% or less, and the low-risk limits have 4% or lower estimated risk. The results support current clinical practice, with some possibility for dose escalation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: 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.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.

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 V(50%) and mean V(100%) 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 V(5%) and mean V(30%) to the contralateral and ipsilateral lungs were 1.0 ± 1.6% and 1.3 ± 1.2%, respectively. In our study, the mean V(5%) 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 V(20%) to V(100%) of the breast from CyberKnife planning was the smallest. The heart and lung doses were similar in all the techniques except that the V(5%) 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.

Purpose: To quantify the target and normal structures on dose distributing variations during intensity-modulated radiotherapy (IMRT) and to assess the value of replanning for nasopharyngeal carcinoma (NPC) patients., Methods and Materials: Twenty-eight NPC patients treated with IMRT were recruited. The IMRT was delivered in 33 fractions, to 70 to 76Gy, to the gross tumor volume (GTV). Before the 25th fraction of IMRT, a new simulation computed tomography (CT) scan was acquired for all patients. According to the dose constraint criterion in the Radiation Therapy Oncology Group (RTOG) 0225 protocol, the replanning was generated on the new simulation CT. With the Quality Assessment Center of a CORVUS 6.3 treatment planning system, a phantom plan was generated for each patient by applying the beam configurations of the initial plan to the anatomy of the new simulation CT. The dose-volume histograms of the phantom plan were compared with the replanning., Results: The percentage of prescription dose delivered to the clinical target volume (CTV1) was significantly increased by 4.91% +/- 10.89%, whereas the maximum dose to the spinal cord, mean dose to the left parotid, and V30 to the right parotid were significantly decreased by 5.00 +/- 9.23Gy, 4.23 +/- 10.03Gy, and 11.47% +/- 18.89% respectively in the replanning, compared with the phantom plan (p < 0.05). Based on the dose constraint criterion in the RTOG0225 protocol, 50% of phantom plans (14/28) were out of limit for the dose to the normal critical structures, whereas no plan was out of limit in replanning (p < 0.001)., Conclusion: Replanning for patients with NPC before the 25th fraction during IMRT helps to ensure adequate dose to the target volumes and safe doses to critical normal structures., (Copyright 2010 Elsevier Inc. All rights reserved.)

Current gated radiation therapy starts with simulation 4DCT images of a patient with lung cancer. We propose a method to confirm the phase of 4DCT for planning and setup position at the time of treatment. An intensity-based rigid algorithm was developed in this work to register an orthogonal set of on-board projection X-ray images with each phase of the 4DCT. Multiple DRRs for one of ten 4DCT phases are first generated and the correlation coefficient (CC) between the projection X-ray image and each DRR is computed. The maximum value of CC for the phase is found via a simulated annealing optimization process. The whole process repeats for all ten phases. The 4DCT phase that has the highest CC is identified as the breathing phase of the X-ray. The phase verification process is validated by a moving phantom study. Thus, the method may be used to independently confirm the correspondence between the gating phase at the times of 4DCT simulation and radiotherapy delivery. When the intended X-ray phase and actual gating phase are consistent, the registration of the DRRs and the projection images may also yield the values of patient shifts for treatment setup. This method could serve as the 4D analog of the conventional setup film as it provides both verification of the specific phase at the time of treatment and isocenter positioning shifts for treatment delivery.

Respiratory gating and tumor tracking for dynamic multileaf collimator delivery require accurate and real-time localization of the lung tumor position during treatment. Deriving tumor position from external surrogates such as abdominal surface motion may have large uncertainties due to the intra- and interfraction variations of the correlation between the external surrogates and internal tumor motion. Implanted fiducial markers can be used to track tumors fluoroscopically in real time with sufficient accuracy. However, it may not be a practical procedure when implanting fiducials bronchoscopically. In this work, a method is presented to track the lung tumor mass or relevant anatomic features projected in fluoroscopic images without implanted fiducial markers based on an optical flow algorithm. The algorithm generates the centroid position of the tracked target and ignores shape changes of the tumor mass shadow. The tracking starts with a segmented tumor projection in an initial image frame. Then, the optical flow between this and all incoming frames acquired during treatment delivery is computed as initial estimations of tumor centroid displacements. The tumor contour in the initial frame is transferred to the incoming frames based on the average of the motion vectors, and its positions in the incoming frames are determined by fine-tuning the contour positions using a template matching algorithm with a small search range. The tracking results were validated by comparing with clinician determined contours on each frame. The position difference in 95% of the frames was found to be less than 1.4 pixels (approximately 0.7 mm) in the best case and 2.8 pixels (approximately 1.4 mm) in the worst case for the five patients studied.

A dynamic multi-leaf collimator (DMLC) can be used to track a moving target during radiotherapy. One of the major benefits for DMLC tumor tracking is that, in addition to the compensation for tumor translational motion, DMLC can also change the aperture shape to conform to a deforming tumor projection in the beam's eye view. This paper presents a method that can track a deforming lung tumor in fluoroscopic video using active shape models (ASM) (Cootes et al 1995 Comput. Vis. Image Underst. 61 38-59). The method was evaluated by comparing tracking results against tumor projection contours manually edited by an expert observer. The evaluation shows the feasibility of using this method for precise tracking of lung tumors with deformation, which is important for DMLC-based real-time tumor tracking.

This paper proposes a novel respiratory detection method based on diaphragm motion measurements using a 2D ultrasound unit. The proposed method extracts a respiratory signal from an automated analysis of the internal diaphragm motion during breathing. The respiratory signal may be used for gating. Ultrasound studies of diaphragm breathing motion were performed on four volunteers. The ultrasound video stream was captured and transferred to a personal computer and decomposed into individual image frames. After straightforward image analysis, region of interest selection, and filtering, the mutual information (MI) and correlation coefficients (CCs) between a selected reference frame and all other frames were computed. The resulting MI and CC values were discovered to produce a signal corresponding to the respiratory cycle in both phase and magnitude. We also studied the diaphragm motion of two volunteers during repeated deep inspiration breath holds (DIBH) and found a slight relaxation motion of the diaphragm during the DIBH, suggesting that the residual motion may be important for treatments delivered at this breathing phase. Applying the proposed respiratory detection method to these ultrasound studies, we found that the MI and CC values demonstrate the relaxation behavior, indicatingthat our method may be used to determine the radiation triggering time for a DIBH technique.