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Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies.
Kaiser A, Eley JG, Onyeuku NE, Rice SR, Wright CC, McGovern NE, Sank M, Zhu M, Vujaskovic Z, Simone CB, Hussain A
(2019) J Vis Exp :
MeSH Terms: Humans, Male, Photons, Prostatic Neoplasms, Proton Therapy, Radiometry, Radiotherapy Planning, Computer-Assisted
Show Abstract · Added March 30, 2020
Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.
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Efficient Interplay Effect Mitigation for Proton Pencil Beam Scanning by Spot-Adapted Layered Repainting Evenly Spread out Over the Full Breathing Cycle.
Poulsen PR, Eley J, Langner U, Simone CB, Langen K
(2018) Int J Radiat Oncol Biol Phys 100: 226-234
MeSH Terms: Bronchial Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Exhalation, Four-Dimensional Computed Tomography, Humans, Inhalation, Kidney Neoplasms, Liver Neoplasms, Lung Neoplasms, Neoplasms, Organ Motion, Pancreatic Neoplasms, Proton Therapy, Radiotherapy Planning, Computer-Assisted, Respiration, Software, Time Factors
Show Abstract · Added March 30, 2020
PURPOSE - To develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS).
METHODS AND MATERIALS - A new flexible repainting scheme with spot-adapted numbers of repainting evenly spread out over the whole breathing cycle (assumed to be 4 seconds) was developed. Twelve fields from 5 thoracic and upper abdominal PBS plans were delivered 3 times using the new repainting scheme to an ion chamber array on a motion stage. One time was static and 2 used 4-second, 3-cm peak-to-peak sinusoidal motion with delivery started at maximum inhalation and maximum exhalation. For comparison, all dose measurements were repeated with no repainting and with 8 repaintings. For each motion experiment, the 3%/3-mm gamma pass rate was calculated using the motion-convolved static dose as the reference. Simulations were first validated with the experiments and then used to extend the study to 0- to 5-cm motion magnitude, 2- to 6-second motion periods, patient-measured liver tumor motion, and 1- to 6-fraction treatments. The effect of the proposed method was evaluated for the 5 clinical cases using 4-dimensional (4D) dose reconstruction in the planning 4D computed tomography scan. The target homogeneity index, HI = (D - D)/D, of a single-fraction delivery is reported, where D and D is the dose delivered to 2% and 98% of the target, respectively, and D is the mean dose.
RESULTS - The gamma pass rates were 59.6% ± 9.7% with no repainting, 76.5% ± 10.8% with 8 repaintings, and 92.4% ± 3.8% with the new repainting scheme. Simulations reproduced the experimental gamma pass rates with a 1.3% root-mean-square error and demonstrated largely improved gamma pass rates with the new repainting scheme for all investigated motion scenarios. One- and two-fraction deliveries with the new repainting scheme had gamma pass rates similar to those of 3-4 and 6-fraction deliveries with 8 repaintings. The mean HI for the 5 clinical cases was 14.2% with no repainting, 13.7% with 8 repaintings, 12.0% with the new repainting scheme, and 11.6% for the 4D dose without interplay effects.
CONCLUSIONS - A novel repainting strategy for efficient interplay effect mitigation was proposed, implemented, and shown to outperform conventional repainting in experiments, simulations, and dose reconstructions. This strategy could allow for safe and more optimal clinical delivery of thoracic and abdominal proton PBS and better facilitate hypofractionated and stereotactic treatments.
Copyright © 2017 Elsevier Inc. All rights reserved.
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A comparative analysis between sequential boost and integrated boost intensity-modulated radiation therapy with concurrent chemotherapy for locally-advanced head and neck cancer.
Vlacich G, Stavas MJ, Pendyala P, Chen SC, Shyr Y, Cmelak AJ
(2017) Radiat Oncol 12: 13
MeSH Terms: Adult, Aged, Aged, 80 and over, Chemoradiotherapy, Cohort Studies, Disease-Free Survival, Female, Head and Neck Neoplasms, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Radiotherapy, Intensity-Modulated, Retrospective Studies
Show Abstract · Added April 18, 2017
BACKGROUND - Planning and delivery of IMRT for locally advanced head and neck cancer (LAHNC) can be performed using sequential boost or simultaneous integrated boost (SIB). Whether these techniques differ in treatment-related outcomes including survival and acute and late toxicities remain largely unexplored.
METHODS - We performed a single institutional retrospective matched cohort analysis on patients with LAHNC treated with definitive chemoradiotherapy to 69.3 Gy in 33 fractions. Treatment was delivered via sequential boost (n = 68) or SIB (n = 141). Contours, plan evaluation, and toxicity assessment were performed by a single experienced physician. Toxicities were graded weekly during treatment and at 3-month follow up intervals. Recurrence-free survival, disease-free survival, and overall survival were estimated via Kaplan-Meier statistical method.
RESULTS - At 4 years, the estimated overall survival was 69.3% in the sequential boost cohort and 76.8% in the SIB cohort (p = 0.13). Disease-free survival was 63 and 69% respectively (p = 0.27). There were no significant differences in local, regional or distant recurrence-free survival. There were no significant differences in weight loss (p = 0.291), gastrostomy tube placement (p = 0.494), or duration of gastrostomy tube dependence (p = 0.465). Rates of acute grade 3 or 4 dysphagia (82% vs 55%) and dermatitis (78% vs 58%) were significantly higher in the SIB group (p < 0.001 and p = 0.012 respectively). Moreover, a greater percentage of the SIB cohort did not receive the prescribed dose due to acute toxicity (7% versus 0, p = 0.028).
CONCLUSIONS - There were no differences in disease related outcomes between the two treatment delivery approaches. A higher rate of grade 3 and 4 radiation dermatitis and dysphagia were observed in the SIB group, however this did not translate into differences in late toxicity. Additional investigation is necessary to further evaluate the acute toxicity differences.
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Margin of error for a frameless image guided radiosurgery system: Direct confirmation based on posttreatment MRI scans.
Luo G, Neimat JS, Cmelak A, Kirschner AN, Attia A, Morales-Paliza M, Ding GX
(2017) Pract Radiat Oncol 7: e223-e231
MeSH Terms: Brain, Essential Tremor, Female, Humans, Magnetic Resonance Imaging, Male, Margins of Excision, Parkinson Disease, Quality Control, Radiosurgery, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Thalamus
Show Abstract · Added April 2, 2019
PURPOSE - To report on radiosurgery delivery positioning accuracy in the treatment of tremor patients with frameless image guided radiosurgery using the linear accelerator (LINAC) based ExacTrac system and to describe quality assurance (QA) procedures used.
METHODS AND MATERIALS - Between 2010 and 2015, 20 patients underwent radiosurgical thalamotomy targeting the ventral intermediate nucleus for the treatment of severe tremor. The median prescription dose was 140 Gy (range, 120-145 Gy) in a single fraction. The median maximum dose was 156 Gy (range, 136-162 Gy). All treatment planning was performed with the iPlan system using a 4-mm circular cone with multiple arcs. Before each treatment, QA procedures were performed, including the imaging system. As a result of the extremely high dose delivered in a single fraction, a well-defined circular mark developed on the posttreatment magnetic resonance imaging (MRI). Eight of these 20 patients were selected to evaluate treatment localization errors because their circular marks were available in posttreatment MRI. In this study, the localization error is defined as the distance between the center of the intended target and the center of the posttreatment mark.
RESULTS - The mean error of distance was found to be 1.1 mm (range, 0.4-1.5 mm). The mean errors for the left-right, anteroposterior, and superoinferior directions are 0.5 mm, 0.6 mm, and 0.7 mm, respectively.
CONCLUSIONS - The result reported in this study includes all tremor patients treated at our institution when their posttreatment MRI data were available for study. It represents a direct confirmation of target positioning accuracy in radiosurgery with a LINAC-based frameless system and its limitations. This level of accuracy is only achievable with an appropriate QA program in place for a LINAC-based frameless radiosurgery system.
Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
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Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy.
Eley JG, Friedrich T, Homann KL, Howell RM, Scholz M, Durante M, Newhauser WD
(2016) Int J Radiat Oncol Biol Phys 95: 279-286
MeSH Terms: Breast, Breast Neoplasms, Carbon, Esophagus, Female, Heart, Heavy Ion Radiotherapy, Hodgkin Disease, Humans, Incidence, Linear Models, Lung, Neoplasms, Second Primary, Organs at Risk, Proton Therapy, Radiography, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Relative Biological Effectiveness, Risk Assessment, Sensitivity and Specificity, Spinal Cord, Uncertainty
Show Abstract · Added March 30, 2020
PURPOSE - This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients.
METHODS AND MATERIALS - We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model.
RESULTS - For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180).
CONCLUSIONS - Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy.
Copyright © 2016 Elsevier Inc. All rights reserved.
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Validation of a track repeating algorithm for intensity modulated proton therapy: clinical cases study.
Yepes PP, Eley JG, Liu A, Mirkovic D, Randeniya S, Titt U, Mohan R
(2016) Phys Med Biol 61: 2633-45
MeSH Terms: Algorithms, Female, Humans, Male, Neoplasms, Proton Therapy, Radiotherapy Planning, Computer-Assisted, Radiotherapy, Intensity-Modulated
Show Abstract · Added March 30, 2020
Monte Carlo (MC) methods are acknowledged as the most accurate technique to calculate dose distributions. However, due its lengthy calculation times, they are difficult to utilize in the clinic or for large retrospective studies. Track-repeating algorithms, based on MC-generated particle track data in water, accelerate dose calculations substantially, while essentially preserving the accuracy of MC. In this study, we present the validation of an efficient dose calculation algorithm for intensity modulated proton therapy, the fast dose calculator (FDC), based on a track-repeating technique. We validated the FDC algorithm for 23 patients, which included 7 brain, 6 head-and-neck, 5 lung, 1 spine, 1 pelvis and 3 prostate cases. For validation, we compared FDC-generated dose distributions with those from a full-fledged Monte Carlo based on GEANT4 (G4). We compared dose-volume-histograms, 3D-gamma-indices and analyzed a series of dosimetric indices. More than 99% of the voxels in the voxelized phantoms describing the patients have a gamma-index smaller than unity for the 2%/2 mm criteria. In addition the difference relative to the prescribed dose between the dosimetric indices calculated with FDC and G4 is less than 1%. FDC reduces the calculation times from 5 ms per proton to around 5 μs.
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Risk-optimized proton therapy to minimize radiogenic second cancers.
Rechner LA, Eley JG, Howell RM, Zhang R, Mirkovic D, Newhauser WD
(2015) Phys Med Biol 60: 3999-4013
MeSH Terms: Algorithms, Dose Fractionation, Radiation, Humans, Male, Middle Aged, Neoplasms, Radiation-Induced, Prostatic Neoplasms, Proton Therapy, Radiotherapy Planning, Computer-Assisted, Risk
Show Abstract · Added March 30, 2020
Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment planning utilized a combination of a commercial treatment planning system and an in-house risk-optimization algorithm. When normal-tissue dose constraints were incorporated in treatment planning, the risk model that incorporated the effects of fractionation, initiation, inactivation, repopulation and promotion selected a combination of anterior and lateral beams, which lowered the relative risk by 21% for the bladder and 30% for the rectum compared to the lateral-opposed beam arrangement. Other results were found for other risk models.
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Robustness of target dose coverage to motion uncertainties for scanned carbon ion beam tracking therapy of moving tumors.
Eley JG, Newhauser WD, Richter D, Lüchtenborg R, Saito N, Bert C
(2015) Phys Med Biol 60: 1717-40
MeSH Terms: Heavy Ion Radiotherapy, Humans, Lung Neoplasms, Motion, Radiation Monitoring, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Uncertainty
Show Abstract · Added March 30, 2020
Beam tracking with scanned carbon ion radiotherapy achieves highly conformal target dose by steering carbon pencil beams to follow moving tumors using real-time magnetic deflection and range modulation. The purpose of this study was to evaluate the robustness of target dose coverage from beam tracking in light of positional uncertainties of moving targets and beams. To accomplish this, we simulated beam tracking for moving targets in both water phantoms and a sample of lung cancer patients using a research treatment planning system. We modeled various deviations from perfect tracking that could arise due to uncertainty in organ motion and limited precision of a scanned ion beam tracking system. We also investigated the effects of interfractional changes in organ motion on target dose coverage by simulating a complete course of treatment using serial (weekly) 4DCTs from six lung cancer patients. For perfect tracking of moving targets, we found that target dose coverage was high ([Formula: see text] was 94.8% for phantoms and 94.3% for lung cancer patients, respectively) but sensitive to changes in the phase of respiration at the start of treatment and to the respiratory period. Phase delays in tracking the moving targets led to large degradation of target dose coverage (up to 22% drop for a 15° delay). Sensitivity to technical uncertainties in beam tracking delivery was minimal for a lung cancer case. However, interfractional changes in anatomy and organ motion led to large decreases in target dose coverage (target coverage dropped approximately 8% due to anatomy and motion changes after 1 week). Our findings provide a better understand of the importance of each of these uncertainties for beam tracking with scanned carbon ion therapy and can be used to inform the design of future scanned ion beam tracking systems.
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A 4D-optimization concept for scanned ion beam therapy.
Graeff C, Lüchtenborg R, Eley JG, Durante M, Bert C
(2013) Radiother Oncol 109: 419-24
MeSH Terms: Carcinoma, Non-Small-Cell Lung, Four-Dimensional Computed Tomography, Heavy Ion Radiotherapy, Humans, Ions, Lung Neoplasms, Motion, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Radiotherapy, Conformal
Show Abstract · Added March 30, 2020
BACKGROUND AND PURPOSE - Scanned carbon beam therapy offers advantageous dose distributions and an increased biological effect. Treating moving targets is complex due to sensitivity to range changes and interplay. We propose a 4D treatment planning concept that considers motion during particle number optimization.
MATERIAL AND METHODS - The target was subdivided into sectors, one for each motion phase of a 4D-CT. Each sector was non-rigidly transformed to its motion phase and there targeted by a dedicated raster field (RST). Therefore, the resulting 4D-RST compensated target motion and range changes. A 4D treatment control system (TCS) was needed for synchronized delivery to the measured patient motion. 4D-optimized plans were simulated for 9 NSCLC lung cancer patients and compared to static irradiation at end-exhale. A prototype TCS was implemented and successfully tested in a film experiment.
RESULTS - The 4D-optimized treatment plan resulted in only slightly lower dose coverage of the target compared to static optimization, with V 95% of 97.9% (median, range 96.5-99.4%) vs. 99.3% (98.5-99.8%), with negligible overdose. The conformity number was comparable at 88.2% (85.1-92.5%) vs. 85.2% (79.9-91.2%) for 4D and static, respectively.
CONCLUSION - We implemented and tested a 4D treatment plan optimization method resulting in highly conformal dose delivery.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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Segmentation editing improves efficiency while reducing inter-expert variation and maintaining accuracy for normal brain tissues in the presence of space-occupying lesions.
Deeley MA, Chen A, Datteri RD, Noble J, Cmelak A, Donnelly E, Malcolm A, Moretti L, Jaboin J, Niermann K, Yang ES, Yu DS, Dawant BM
(2013) Phys Med Biol 58: 4071-97
MeSH Terms: Algorithms, Brain, Brain Neoplasms, Humans, Image Processing, Computer-Assisted, Radiotherapy Planning, Computer-Assisted, Randomized Controlled Trials as Topic, Tomography, X-Ray Computed
Show Abstract · Added February 19, 2015
Image segmentation has become a vital and often rate-limiting step in modern radiotherapy treatment planning. In recent years, the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumours in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: simultaneous truth and performance level estimation and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers' segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy.
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8 MeSH Terms