Publications by authors named "Jinyu Xue"

37 Publications

Misalignment Fault Diagnosis for Wind Turbines Based on Information Fusion.

Entropy (Basel) 2021 Feb 20;23(2). Epub 2021 Feb 20.

School of Mechanical, Electronic and Control Engineering, Beijing Jiaotong University, Beijing 100044, China.

Most conventional wind turbine fault diagnosis techniques only use a single type of signal as fault feature and their performance could be limited to such signal characteristics. In this paper, multiple types of signals including vibration, temperature, and stator current are used simultaneously for wind turbine misalignment diagnosis. The model is constructed by integrated methods based on Dempster-Shafer (D-S) evidence theory. First, the time domain, frequency domain, and time-frequency domain features of the collected vibration, temperature, and stator current signal are respectively taken as the inputs of the least square support vector machine (LSSVM). Then, the LSSVM outputs the posterior probabilities of the normal, parallel misalignment, angular misalignment, and integrated misalignment of the transmission systems. The posterior probabilities are used as the basic probabilities of the evidence fusion, and the fault diagnosis is completed according to the D-S synthesis and decision rules. Considering the correlation between the inputs, the vibration and current feature vectors' dimensionalities are reduced by t-distributed stochastic neighbor embedding (t-SNE), and the improved artificial bee colony algorithm is used to optimize the parameters of the LSSVM. The results of the simulation and experimental platform demonstrate the accuracy of the proposed model and its superiority compared with other models.
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http://dx.doi.org/10.3390/e23020243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923760PMC
February 2021

Potential Clinical Significance of Overall Targeting Accuracy and Motion Management in the Treatment of Tumors That Move With Respiration: Lessons Learnt From a Quarter Century of Stereotactic Body Radiotherapy From Dose Response Models.

Front Oncol 2020 9;10:591430. Epub 2021 Feb 9.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States.

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 . 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.
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http://dx.doi.org/10.3389/fonc.2020.591430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900559PMC
February 2021

Initial Data Pooling for Radiation Dose-Volume Tolerance for Carotid Artery Blowout and Other Bleeding Events in Hypofractionated Head and Neck Retreatments.

Int J Radiat Oncol Biol Phys 2021 Feb 11. Epub 2021 Feb 11.

Department of Radiation Oncology, Bon Secours Mercy Health System, Youngstown, Ohio.

Purpose: Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized.

Methods And Materials: A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed.

Results: Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT.

Conclusions: Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.037DOI Listing
February 2021

Stereotactic Body Radiation Therapy for Spinal Metastases: Tumor Control Probability Analyses and Recommended Reporting Standards.

Int J Radiat Oncol Biol Phys 2021 Jan 27. Epub 2021 Jan 27.

Department of Radiation Oncology, University of California at Davis, Sacramento, California.

Purpose: We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions.

Methods And Materials: PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose.

Results: Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated α/β = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions.

Conclusions: Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.021DOI Listing
January 2021

Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases.

Int J Radiat Oncol Biol Phys 2020 Dec 31. Epub 2020 Dec 31.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature.

Methods And Materials: PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference.

Results: Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter.

Conclusions: TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.034DOI Listing
December 2020

Stereotactic Radiosurgery for Vestibular Schwannomas: Tumor Control Probability Analyses and Recommended Reporting Standards.

Int J Radiat Oncol Biol Phys 2020 Dec 26. Epub 2020 Dec 26.

Machine Learning Department, Moffitt Cancer Center, Tampa, Florida.

Purpose: We sought to investigate the tumor control probability (TCP) of vestibular schwannomas after single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2 to 5 fractions (fSRS).

Methods And Materials: Studies (PubMed indexed from 1993-2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions.

Results: Data were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of <11 Gy in a single-fraction, variability in definition of "tumor control," and by lack of significant increase in TCP for doses >12 Gy. Using linear-quadratic-based dose conversion, the 3- to 5-year TCP was estimated at 95% at an EQD2 of 25 Gy, corresponding to 1-, 3-, and 5-fraction doses of 13.8 Gy, 19.2 Gy, and 21.5 Gy, respectively. Single-fraction doses of 10 Gy, 11 Gy, 12 Gy, and 13 Gy predicted a TCP of 85.0%, 88.4%, 91.2%, and 93.5%, respectively. For fSRS, 18 Gy in 3 fractions (EQD2 of 23.0 Gy) and 25 Gy in 5 fractions (EQD2 of 30.2 Gy) corresponded to TCP of 93.6% and 97.2%. Overall, the quality of dosimetric reporting was poor; recommended reporting guidelines are presented.

Conclusions: With current typical SRS doses of 12 Gy in 1 fraction, 18 Gy in 3 fractions, and 25 Gy in 5 fractions, 3- to 5-year TCP exceeds 91%. To improve pooled data analyses to optimize treatment outcomes for patients with vestibular schwannoma, future reports of SRS should include complete dosimetric details with well-defined tumor control and toxicity endpoints.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.019DOI Listing
December 2020

Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain.

Int J Radiat Oncol Biol Phys 2020 Sep 11. Epub 2020 Sep 11.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).

Methods And Materials: Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases.

Results: Data from 51 reports are summarized. There was wide variability in reported rates of radionecrosis. Available data for SRS/fSRS for brain metastases were more amenable to NTCP modeling than AVM data. In the setting of brain metastases, SRS/fSRS-associated radionecrosis can be difficult to differentiate from tumor progression. For single-fraction SRS to brain metastases, tissue volumes (including target volumes) receiving 12 Gy (V1) of 5 cm, 10 cm, or >15 cm were associated with risks of symptomatic radionecrosis of approximately 10%, 15%, and 20%, respectively. SRS for AVM was associated with modestly lower rates of symptomatic radionecrosis for equivalent V12. For brain metastases, brain plus target volume V20 (3-fractions) or V24 (5-fractions) <20 cm was associated with <10% risk of any necrosis or edema, and <4% risk of radionecrosis requiring resection.

Conclusions: The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.013DOI Listing
September 2020

Adaptive radiotherapy based on statistical process control for oropharyngeal cancer.

J Appl Clin Med Phys 2020 Sep 8;21(9):171-177. Epub 2020 Aug 8.

Department of Radiation Oncology, NYU Langone Health, New York, NY, USA.

Purpose: The purpose of this study is to quantify dosimetric changes throughout the delivery of oropharyngeal cancer treatment and to investigate the application of statistical process control (SPC) for the management of significant deviations during the course of radiotherapy.

Methods: Thirteen oropharyngeal cancer patients with daily cone beam computed tomography (CBCT) were retrospectively reviewed. Cone beam computed tomography images of every other fraction were imported to the Velocity software and registered to planning CT using the 6 DOF (degrees of freedom) couch shifts generated during patient setup. Using Velocity "Adaptive Monitoring" module, the setup-corrected CBCT was matched to planning CT using a deformable registration. Volumes and dose metrics at each fraction were calculated and rated with plan values to evaluate interfractional dosimetric variations using a SPC framework. T-tests between plan and fraction volumes were performed to find statistically insignificant fractions. Average upper and lower process capacity limits (UCL, LCL) of each dose metric were derived from these fractions using conventional SPC guidelines.

Results: Gross tumor volume (GTV) and organ at risk (OAR) volumes in the first 13 fractions had no significant changes from the pretreatment planning CT. The GTV and the parotid glands subsequently decreased by 10% at the completion of treatment. There were 3-4% increases in parotid mean doses, but no significant differences in dose metrics of GTV and other OARs. The changes were organ and patient dependent. Control charts for various dose metrics were generated to assess the metrics at each fraction for individual patient.

Conclusions: Daily CBCT could be used to monitor dosimetric variations of targets and OARs resulting from volume changes and tissue deformation in oropharyngeal cancer radiotherapy. Treatment review with the guidance of a SPC tool allows for an objective and consistent clinical decision to apply adaptive radiotherapy.
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http://dx.doi.org/10.1002/acm2.12993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497930PMC
September 2020

Improved Dose Conformity for Adjacent Targets: A Novel Planning Technique for Gamma Knife Stereotactic Radiosurgery.

Cureus 2018 Jul 27;10(7):e3057. Epub 2018 Jul 27.

Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, USA.

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).
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http://dx.doi.org/10.7759/cureus.3057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168383PMC
July 2018

Dosimetric assessment of tumor control probability in intensity and volumetric modulated radiotherapy plans.

Br J Radiol 2019 Feb 21;92(1094):20180471. Epub 2018 Sep 21.

Department of Radiation Oncology, NYU Langone Health & Laura and Isaac Perlmutter Cancer Center , New York, NY , USA.

Objective:: Radiobiological models have been used to calculate the outcomes of treatment plans based on dose-volume relationship. This study examines several radiobiological models for the calculation of tumor control probability (TCP) of intensity modulated radiotherapy plans for the treatment of lung, prostate, and head and neck (H&N) cancers.

Methods:: Dose volume histogram (DVH) data from the intensity modulated radiotherapy plans of 36 lung, 26 prostate, and 87  H&N cases were evaluated. The Poisson, Niemierko, and Marsden models were used to calculate the TCP of each disease group treatment plan. The calculated results were analyzed for correlation and discrepancy among the three models, as well as different treatment sites under study.

Results:: The median value of calculated TCP in lung plans was 61.9% (34.1-76.5%), 59.5% (33.5-73.9%) and 32.5% (0.0-93.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in prostate plans was 85.1% (56.4-90.9%), 81.2% (56.1-88.7%) and 62.5% (28.2-75.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in H&N plans was 94.0% (44.0-97.8%) and 94.3% (0.0-97.8%) with the Poisson and Niemierko models, respectively. There were significant differences between the calculated TCPs with the Marsden model in comparison with either the Poisson or Niemierko model (p < 0.001) for both lung and prostate plans. The TCPs calculated by the Poisson and Niemierko models were significantly correlated for all three tumor sites.

Conclusion:: There are variations with different radiobiological models. Understanding of the correlation and limitation of a TCP model with dosimetric parameters can help develop the meaningful objective functions for plan optimization, which would lead to the implementation of outcome-based planning. More clinical data are needed to refine and consolidate the model for accuracy and robustness.

Advances In Knowledge:: This study has tested three radiobiological models with varied disease sites. It is significant to compare different models with the same data set for better understanding of their clinical applicability.
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http://dx.doi.org/10.1259/bjr.20180471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404826PMC
February 2019

A Practical Method to Optimize Quality Assurance Results of Arc Therapy Plans in Beam Modeling.

J Med Phys 2018 Apr-Jun;43(2):106-111

Department of Radiation Oncology, NYU Langone Medical Center, New York 10016, USA.

Dosimetric accuracy of a volumetric modulated arc therapy (VMAT) plan is directly related to the beam model, particularly with multileaf collimator characterization. Inappropriate dosimetric leaf gap (DLG) value can lead to a suboptimal beam model, with significant failure in patient-specific quality assurance (PSQA) of VMAT plans. This study addressed the systematic issue of beam modeling and developed a practical method to determine the optimal DLG value for a beam model. Several complex VMAT plans were selected for the quality assurance analysis using the variable DLG values. The results of three-dimensional (3D) Gamma analysis as a function of the DLG at 3%/3 mm, 2%/2 mm, and 1%/1 mm criteria were fitted by a polynomial curve. The DLG value corresponding to the maximum Gamma passing rate for each polynomial fitting function was derived, and the average was calculated to be the optimal DLG value for each model. The 3D Gamma analysis was repeated with the optimal DLG value to verify the dosimetric accuracy of each VMAT case by PSQA. Gamma passing rates are seen to vary considerably with the DLG values and different analysis criteria (3%/3 mm, 2%/2 mm, and 1%/1 mm) for each case. The optimal DLG derived for each model was 1.16 mm and 1.10 mm, much larger than the measured value (about 0.3 mm). The beam models with the optimal DLG was able to produce an average Gamma passing rate of 97.1% (range, 94.6%- 99.1%) at 3%/3 mm and 93.5% (range, 89.0%- 96.5%) at 2%/2 mm for one beam model, and 97.1% (range, 94.8%- 99.1%) at 3%/3 mm, and 93.3% (range, 88.8%- 96.7%) at 2%/2 mm for another. The overall accuracy of dose calculation for VMAT plans should be optimized with a compromise of varied modulation complexities in a beam model. We have developed a practical method to derive the optimal DLG value for each beam model based on the Gamma passing criterion. This technique should be applicable in general for all beam energies and patient cases.
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http://dx.doi.org/10.4103/jmp.JMP_144_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020624PMC
July 2018

Single- and Multi-Fraction Stereotactic Radiosurgery Dose Tolerances of the Optic Pathways.

Int J Radiat Oncol Biol Phys 2018 Jan 31. Epub 2018 Jan 31.

Department of Radiation Oncology, Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina.

Purpose: Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation.

Methods And Materials: Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION).

Results: Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy.

Conclusions: Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS.
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http://dx.doi.org/10.1016/j.ijrobp.2018.01.053DOI Listing
January 2018

Head and Neck Tumor Control Probability: Radiation Dose-Volume Effects in Stereotactic Body Radiation Therapy for Locally Recurrent Previously-Irradiated Head and Neck Cancer: Report of the AAPM Working Group.

Int J Radiat Oncol Biol Phys 2018 Jan 31. Epub 2018 Jan 31.

Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address:

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as a viable reirradiation strategy for locally recurrent previously-irradiated head and neck cancer. Doses in the literature have varied, which challenges clinical application of SBRT as well as clinical trial design.

Material & Methods: A working group was formed through the American Association of Physicists in Medicine to study tumor control probabilities for SBRT in head and neck cancer. We herein present a systematic review of the available literature addressing the dose/volume data for tumor control probability with SBRT in patients with locally recurrent previously-irradiated head and neck cancer. Dose-response models are generated that present tumor control probability as a function of dose.

Results: Data from more than 300 cases in 8 publications suggest that there is a dose-response relationship, with superior local control and possibly improved overall survival for doses of 35 to 45 Gy (in 5 fractions) compared with <30 Gy.

Conclusion: Stereotactic body radiation therapy doses equivalent to 5-fraction doses of 40 to 50 Gy are suggested for retreatment.
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http://dx.doi.org/10.1016/j.ijrobp.2018.01.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294512PMC
January 2018

Chemosensitive Phox2b-expressing neurons are crucial for hypercapnic ventilatory response in the nucleus tractus solitarius.

J Physiol 2017 07 16;595(14):4973-4989. Epub 2017 Jun 16.

Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei, China.

Key Points: Central hypercapnic hypoventilation is highly prevalent in children suffering from congenital central hypoventilation syndrome (CCHS). Mutations of the gene for paired-like homeobox 2b (Phox2b) are aetiologically associated with CCHS and Phox2b is present in central components of respiratory chemoreflex, such as the nucleus tractus solitarius (NTS). Injection of the neurotoxin substance P-saporin into NTS destroys Phox2b-expressing neurons. Impaired hypercapnic ventilatory response caused by this neurotoxin is attributable to a loss of CO -sensitive Phox2b-expressing NTS neurons. A subgroup of Phox2b-expressing neurons exhibits intrinsic chemosensitivity. A background K channel-like current is partially responsible for such chemosensitivity in Phox2b-expressing neurons. The present study helps us better understand the mechanism of respiratory deficits in CCHS and potentially locates a brainstem site for development of precise clinical intervention.

Abstract: The nucleus tractus solitarius (NTS) neurons have been considered to function as central respiratory chemoreceptors. However, the common molecular marker defined for these neurons remains unknown. The present study investigated whether paired-like homeobox 2b (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR) and whether these neurons exhibit intrinsic chemosensitivity. HCVR was assessed using whole body plethysmography and neuronal chemosensitivity was examined by patch clamp recordings in brainstem slices or dissociated neurons from Phox2b-EGFP transgenic mice. Injection of the neurotoxin substance P-saporin (SSP-SAP) into NTS destroyed Phox2b-expressing neurons. Minute ventilation and tidal volume were both reduced by 13% during exposure to 8% CO in inspired air when ∼13% of the Phox2b-expressing neurons were eliminated. However, a loss of ∼18% of these neurons was associated with considerable decreases in minute ventilation by ≥18% and in tidal volume by≥22% when challenged by ≥4% CO . In both cases, breathing frequency was unaffected. Most CO -activated neurons were immunoreactive to Phox2b. In brainstem slices, ∼43% of Phox2b-expressing neurons from Phox2b-EGFP mice displayed a sustained or transient increase in firing rate during physiological acidification (pH 7.0 or 8% CO ). Such a response was also present in dissociated neurons in favour of an intrinsic property. In voltage clamp recordings, a background K channel-like current was found in a subgroup of Phox2b-expressing neurons. Thus, the respiratory deficits caused by injection of SSP-SAP into the NTS are attributable to proportional lesions of CO /H -sensitive Phox2b-expressing neurons.
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http://dx.doi.org/10.1113/JP274437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509882PMC
July 2017

Small field dose measurements using plastic scintillation detector in heterogeneous media.

Med Phys 2017 Jul 21;44(7):3815-3820. Epub 2017 May 21.

Department of Radiation Oncology, NYU Langone Medical Center, New York, NY, 10016, USA.

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.
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http://dx.doi.org/10.1002/mp.12272DOI Listing
July 2017

Effect of beam profile measurement on arc therapy plan quality assurance: a case study.

J Appl Clin Med Phys 2017 May 29;18(3):52-55. Epub 2017 Mar 29.

Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, 2 Cooper Plaza, Camden, NJ, 08103, USA.

We present an example when profile measurement and modeling of an Elekta Agility multileaf collimator (MLC) had a large effect specifically on arc therapy plan quality assurance (QA) results using ArcCheck. ArcCheck absolute dose measurements of these plans were systematically lower than planned by 3-10%. Failing QA results were seen even with unmodulated static and conformal arcs. Furthermore, the effect was found to be dependent on collimator angle, with worse results associated with near-zero collimator angles. In contrast, step-and-shoot QA results were not affected. Changing the beam model to match steeper profile measurements obtained using a different measurement device resolved the problem. This case study demonstrates that conventional gamma index analysis can be sensitive to small profile modeling changes.
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http://dx.doi.org/10.1002/acm2.12071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689840PMC
May 2017

Simple Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies.

Int J Radiat Oncol Biol Phys 2016 08 25;95(5):1357-1366. Epub 2016 Mar 25.

Department of Radiation Oncology, GRU Cancer Center/Medical College of Georgia, Georgia Regents University, Augusta, Georgia; Currently at Department of Radiation Oncology, Simon Cancer Center, Indiana University Medical School, Indianapolis, Indiana. Electronic address:

Purpose: To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiation therapy (SBRT) of the thorax.

Methods And Materials: Published studies on lung toxicity in patients with early-stage non-small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT, including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2 to 5 (G2+) and grade 3 to 5 (G3+) RILT were computed. Patient, tumor, and dosimetric factors were analyzed for their correlation with RILT.

Results: Eighty-eight studies (7752 patients) that reported RILT incidence were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% confidence interval [CI]: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range, 1.4-4.1) cm. Among the factors analyzed, older patient age (P=.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P=.049) and G3+ RILT (P=.001). Patients with stage IA versus stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, odds ratio = 0.43, 95% CI: 0.29-0.64, P<.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P=.027) and V20 (P=.019) in patients with G2+ RILT than in those with grade 0 to 1 RILT.

Conclusions: The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD, also significantly affect RILT risk.
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http://dx.doi.org/10.1016/j.ijrobp.2016.03.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541363PMC
August 2016

Stereotactic Radiosurgery for Poor Performance Status Patients.

Int J Radiat Oncol Biol Phys 2016 07 16;95(3):956-959. Epub 2016 Feb 16.

Department of Neurological Surgery, Cooper University Hospital, Camden, New Jersey.

Purpose: Patients with poor performance status (PS), usually defined as a Karnofsky Performance Status of 60 or less, were not eligible for randomized stereotactic radiosurgery (SRS) studies, and many guidelines suggest that whole-brain radiation therapy (WBRT) is the most appropriate treatment for poor PS patients.

Methods And Materials: In this retrospective review of our SRS database, we identified 36 patients with PS of 60 or less treated with SRS for central nervous system (CNS) metastatic disease. PS, as defined by the Karnofsky Performance Status, was 60 (27 patients), 50 (8 patients), or 40 (1 patient). The median number of CNS lesions treated was 3.

Results: Median overall survival (OS) was 7.2 months (range, 0.73-25.6 months). Fifteen patients (41%) were alive at 6 months, and 6 patients (16.6%) were alive at 1 year. There was no difference in OS in patients who underwent previous WBRT. There were no local failures or cases of radiation toxicity. Distant CNS failures were seen in 9 patients (25%).

Conclusions: Our patients with poor PS had reasonable median OS and relatively low distant CNS failure rates. Patients in this patient population may be ideal candidates for SRS compared with WBRT given the low incidence of distant failure over their remaining lives and the favorable logistics of single-fraction treatment for these patients with debility and their caregivers.
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http://dx.doi.org/10.1016/j.ijrobp.2016.02.041DOI Listing
July 2016

Estimated Risk Level of Unified Stereotactic Body Radiation Therapy Dose Tolerance Limits for Spinal Cord.

Semin Radiat Oncol 2016 Apr 4;26(2):165-71. Epub 2016 Jan 4.

Department of Radiation Oncology, Stanford University, Stanford, CA.

A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation.
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http://dx.doi.org/10.1016/j.semradonc.2015.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990135PMC
April 2016

Small Bowel Dose Tolerance for Stereotactic Body Radiation Therapy.

Semin Radiat Oncol 2016 Apr 4;26(2):157-64. Epub 2015 Dec 4.

MD Anderson at Cooper University Hospital, Camden, NJ. Electronic address:

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.
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http://dx.doi.org/10.1016/j.semradonc.2015.11.009DOI Listing
April 2016

Validity of Current Stereotactic Body Radiation Therapy Dose Constraints for Aorta and Major Vessels.

Semin Radiat Oncol 2016 Apr 24;26(2):135-9. Epub 2015 Dec 24.

MD Anderson Cancer Center, Cooper University Hospital, Camden, NJ.

Understanding dose constraints for critical structures in stereotactic body radiation therapy (SBRT) is essential to generate a plan for optimal efficacy and safety. Published dose constraints are derived by a variety of methods, including crude statistics, actuarial analysis, modeling, and simple biologically effective dose (BED) conversion. Many dose constraints reported in the literature are not consistent with each other, secondary to differences in clinical and dosimetric parameters. Application of a dose constraint without discriminating the variation of all the factors involved may result in suboptimal treatment. This issue of Seminars in Radiation Oncology validates dose tolerance limits for 10 critical anatomic structures based on dose response modeling of clinical outcomes data to include detailed dose-volume metrics. This article presents a logistic dose-response model for aorta and major vessels based on 238 cases from the literature in addition to 387 cases from MD Anderson Cancer Center at Cooper University Hospital, for a total of 625 cases. The Radiation Therapy Oncology Group (RTOG) 0813 dose-tolerance limit of Dmax = 52.5Gy in 5 fractions was found to have a 1.2% risk of grade 3-5 toxicity, and the Timmerman 2008 limit of Dmax = 45Gy in 3 fractions had 2.3% risk. From the model, the 1% and 2% risk levels for D4cc, D1cc, and D0.5cc are also provided in 1-5 fractions, in the form of a dose-volume histogram (DVH) Risk Map.
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http://dx.doi.org/10.1016/j.semradonc.2015.11.001DOI Listing
April 2016

Introduction and Clinical Overview of the DVH Risk Map.

Semin Radiat Oncol 2016 Apr 4;26(2):89-96. Epub 2015 Dec 4.

Department of Radiation Oncology, MD Anderson at Cooper University Hospital, Camden, NJ.

Radiation oncologists need reliable estimates of risk for various fractionation schemes for all critical anatomical structures throughout the body, in a clinically convenient format. Reliable estimation theory can become fairly complex, however, and estimates of risk continue to evolve as the literature matures. To navigate through this efficiently, a dose-volume histogram (DVH) Risk Map was created, which provides a comparison of radiation tolerance limits as a function of dose, fractionation, volume, and risk level. The graphical portion of the DVH Risk Map helps clinicians to easily visualize the trends, whereas the tabular portion provides quantitative precision for clinical implementation. The DVH Risk Map for rib tolerance from stereotactic ablative body radiotherapy (SABR) and stereotactic body radiation therapy (SBRT) is used as an example in this overview; the 5% and 50% risk levels for 1-5 fractions for 5 different volumes are given. Other articles throughout this issue of Seminars in Radiation Oncology present analysis of new clinical datasets including the DVH Risk Maps for other anatomical structures throughout the body.
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http://dx.doi.org/10.1016/j.semradonc.2015.11.005DOI Listing
April 2016

Factors that may determine the targeting accuracy of image-guided radiosurgery.

Med Phys 2015 Oct;42(10):6004-10

Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, New Jersey 08103.

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.
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http://dx.doi.org/10.1118/1.4930961DOI Listing
October 2015

Overview of dosimetric and biological perspectives on radiosurgery of multiple brain metastases in comparison with whole brain radiotherapy.

J Radiosurg SBRT 2015 ;3(4):271-279

Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, NJ 08103, USA.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675494PMC
January 2015

Biological implications of whole-brain radiotherapy versus stereotactic radiosurgery of multiple brain metastases.

J Neurosurg 2014 Dec;121 Suppl:60-8

Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, and.

Object: The efficacy and safety of treatment with whole-brain radiotherapy (WBRT) or with stereotactic radiosurgery (SRS) for multiple brain metastases (> 10) are topics of ongoing debate. This study presents detailed dosimetric and biological information to investigate the possible clinical outcomes of these 2 modalities.

Methods: Five patients with multiple brain metastases (n = 11-23) underwent SRS. Whole-brain radiotherapy plans were 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 radiation doses and biologically effective doses (BEDs) in WBRT and SRS were calculated for each lesion target and for the normal brain tissues for comparison of the 2 modalities in the context of clinical efficacy and published toxicities.

Results: The BEDs targeted to the tumor were higher in SRS than in WBRT by factors ranging from 2.4- to 3.0- fold for the mean dose and from 3.2- to 5.3-fold for the maximum dose. In the 5 patients, mean BEDs in SRS (calculated as percentages of BEDs in WBRT) were 1.3%-34.3% for normal brain tissue, 0.7%-31.6% for the brainstem, 0.5%-5.7% for the chiasm, 0.2%-5.7% for optic nerves, and 0.6%-18.1% for the hippocampus.

Conclusions: The dose-volume metrics presented in this study were essential to understanding the safety and efficacy of WBRT and SRS for multiple brain metastases. Whole-brain radiotherapy results in a higher incidence of radiation-related toxicities than SRS. Even in patients with > 10 brain metastases, the normal CNS tissues receive significantly lower doses in SRS. The mean normal brain dose in SRS correlated with the total volume of the lesions rather than with the number of lesions treated.
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http://dx.doi.org/10.3171/2014.7.GKS141229DOI Listing
December 2014

Low toxicity for lung tumors near the mediastinum treated with stereotactic body radiation therapy.

Pract Radiat Oncol 2013 Apr-Jun;3(2):130-7. Epub 2012 Jun 1.

Department of Radiation Oncology, Cooper University Hospital, One Cooper Plaza, Camden, New Jersey. Electronic address:

Purpose: To report the local control, survival, and low toxicity observed at the Cooper University Hospital CyberKnife Center post stereotactic body radiation therapy (SBRT) in the treatment of lung tumors near the mediastinum.

Methods And Materials: Twenty-four medically inoperable lung cancer patients with tumors near the mediastinum were treated using the Accuray CyberKnife system (Accuray, Sunnyvale, CA) with Monte Carlo dose calculations and heterogeneity corrections from July 2008 to May 2010. The prescription dose ranged from 28.5 Gy to 60 Gy in 3-5 fractions. For conventional fractionation schemes, Emami et al(1) organized the dose tolerance limits into a unified format for clinical utility and partitioned them into 2 risk levels (5% and 50%) with preset volumes for most critical structures throughout the body. In contrast, statistical SBRT dose tolerance limits for mediastinal structures have not been established yet. We have sufficient experience at least to begin organizing a unified format with low-risk and high-risk partitions and preset volumes for 1-5 fractions exposing mediastinal structures. With the help of the (dose-volume histogram) DVH Evaluator, a software tool developed by our senior author, each treatment plan was assessed for safety and feasibility prior to treatment. The DVH Evaluator was also used to analyze the follow-up data and to create graphs of risk, called DVH Risk Maps, superimposing clinical data onto the unified SBRT dose tolerance limits.

Results: It was not feasible to prescribe the doses of peripheral lung lesions for all tumors near the mediastinum because of known toxicity. The crude local tumor control rate achieved in our series was 92%. Median survival was 26.8 months for the primary lung cases and 9.6 months for the metastatic cases. No patients experienced grade 3 or higher toxicities.

Conclusions: We affirm that SBRT is feasible in the treatment of centrally located lung cancers when the dose tolerance limits of critical structures are diligently respected. The low adverse event rates that we have experienced, combined with a good local tumor control rate, are encouraging.
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http://dx.doi.org/10.1016/j.prro.2012.04.007DOI Listing
March 2014

Stereotactic body radiotherapy as an alternative to brachytherapy in gynecologic cancer.

Biomed Res Int 2013 13;2013:898953. Epub 2013 Aug 13.

Department of Radiation Oncology, Cooper University Hospital, Camden, NJ 08103, USA.

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.
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http://dx.doi.org/10.1155/2013/898953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755408PMC
February 2014

Complication probability for radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT).

J Radiosurg SBRT 2013 ;2(2):99-104

Cooper University Hospital, Camden, New Jersey, USA.

Purpose/objective: To determine clinically relevant SBRT/stereotactic ablative radiotherapy (SABR) dose tolerance limits for RP based on statistical analysis of outcomes data.

Materials And Methods: Eighteen consecutive patients who were treated using volumetric modulated arc therapy (RapidArc) for lung tumors exceeding 80cc were assessed. Clinical outcomes have been published elsewhere, and here we present a normal tissue complication probability (NTCP) analysis. The dose volume histogram (DVH) reduction techniques of total lung V20Gy, V15Gy, V10Gy, V5Gy and mean lung dose (MLD) were each analyzed, as well as ipsilateral lung V5Gy and contralateral lung V5Gy, using the DVH Evaluator software tool. The framework of the Lyman Model was used except that each DVH reduction method was analyzed independently instead of using the power-law relationship for volume dependence. Model parameters were fitted using Maximum Likelihood.

Results: RP was reported in 5 patients (CTC Grade 2 in 3, and Grade 3 in 2). Total lung V5Gy and contralateral lung V5Gy were the best predictors of RP (p < 0.0001 for both). For V5Gy, the 10% risk level for Grade 2-3 RP was 27.9% for total lung and 21.8% for contralateral lung. For V20Gy, the 25% risk level is 10.5% of total lung.

Conclusions: Analysis of RP endpoints has identified total lung V5Gy and contralateral lung V5Gy as the best predictors of RP following SBRT when delivered with RapidArc. These findings are based on limited clinical data, and longer follow-up in larger patient cohorts is required in order to determine more accurate dose tolerance limits.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658881PMC
January 2013

Dose-volume effects on brainstem dose tolerance in radiosurgery.

J Neurosurg 2012 Dec;117 Suppl:189-96

Department of Radiation Oncology, Cooper University Hospital, Camden, New Jersey 08103, USA.

Object: Dose-volume data concerning the brainstem in stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN) were analyzed in relation to associated complications. The authors present their set of data and compare it with currently cited information on brainstem dose tolerance associated with conventional fractionated radiation therapy and hypofractionated radiation treatment of other diseases.

Methods: Stereotactic radiosurgery for TN delivers a much higher radiation dose to the brainstem in a single fraction than doses delivered by any other procedures. A literature survey of articles on radiosurgery for TN revealed no incidences of severe toxicity, unlike other high-dose procedures involving the brainstem. Published data on brainstem dose tolerance were investigated and compared with dose-volume data in TN radiosurgery. The authors also performed a biological modeling study of dose-volume data involving the brainstem in cases of TN treated with the Gamma Knife, CyberKnife, and linear accelerator-based systems.

Results: The brainstem may receive a maximum dose as high as 45 Gy during radiosurgery for TN. The major complication after TN radiosurgery is mild to moderate facial numbness, and few other severe toxic responses to radiation are observed. The biologically effective dose of 45 Gy in a single fraction is much higher than any brainstem dose tolerance currently cited in conventional fractionation or in single or hypofractionated radiation treatments. However, in TN radiosurgery, the dose falloff is so steep and the delivery so accurate that brainstem volumes of 0.1-0.5 cm(3) or larger receive lower planned and delivered doses than those in other radiation-related procedures. Current models are suggestive, but an extensive analysis of detailed dose-volume clinical data is needed.

Conclusions: Patients whose TN is treated with radiosurgery are a valuable population in which to demonstrate the dose-volume effects of an extreme hypofractionated radiation treatment on the brainstem. The result of TN radiosurgery suggests that a very small volume of the brainstem can tolerate a drastically high dose without suffering a severe clinical injury. The authors believe that the steep dose gradient in TN radiosurgery plays a key role in the low toxicity experienced by the brainstem.
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http://dx.doi.org/10.3171/2012.7.GKS12962DOI Listing
December 2012

Dosimetric investigation of accelerated partial breast irradiation (APBI) using CyberKnife.

Med Phys 2012 Nov;39(11):6621-8

Department of Radiation Oncology, Cooper University Hospital, Camden, NJ 08103, USA.

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.
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http://dx.doi.org/10.1118/1.4757616DOI Listing
November 2012