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Merging Orthovoltage X-Ray Minibeams spare the proximal tissues while producing a solid beam at the target.
Dilmanian FA, Krishnan S, McLaughlin WE, Lukaniec B, Baker JT, Ailawadi S, Hirsch KN, Cattell RF, Roy R, Helfer J, Kruger K, Spuhler K, He Y, Tailor R, Vassantachart A, Heaney DC, Zanzonico P, Gobbert MK, Graf JS, Nassimi JR, Fatemi NN, Schweitzer ME, Bangiyev L, Eley JG
(2019) Sci Rep 9: 1198
MeSH Terms: Brain Neoplasms, Computer Simulation, Gold, Humans, Metal Nanoparticles, Models, Biological, Monte Carlo Method, Radiography, Radiometry, Radiosurgery, Radiotherapy, Radiotherapy Dosage, X-Ray Therapy, X-Rays
Show Abstract · Added March 30, 2020
Conventional radiation therapy of brain tumors often produces cognitive deficits, particularly in children. We investigated the potential efficacy of merging Orthovoltage X-ray Minibeams (OXM). It segments the beam into an array of parallel, thin (~0.3 mm), planar beams, called minibeams, which are known from synchrotron x-ray experiments to spare tissues. Furthermore, the slight divergence of the OXM array make the individual minibeams gradually broaden, thus merging with their neighbors at a given tissue depth to produce a solid beam. In this way the proximal tissues, including the cerebral cortex, can be spared. Here we present experimental results with radiochromic films to characterize the method's dosimetry. Furthermore, we present our Monte Carlo simulation results for physical absorbed dose, and a first-order biologic model to predict tissue tolerance. In particular, a 220-kVp orthovoltage beam provides a 5-fold sharper lateral penumbra than a 6-MV x-ray beam. The method can be implemented in arc-scan, which may include volumetric-modulated arc therapy (VMAT). Finally, OXM's low beam energy makes it ideal for tumor-dose enhancement with contrast agents such as iodine or gold nanoparticles, and its low cost, portability, and small room-shielding requirements make it ideal for use in the low-and-middle-income countries.
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Spatially fractionated proton minibeams.
Meyer J, Eley J, Schmid TE, Combs SE, Dendale R, Prezado Y
(2019) Br J Radiol 92: 20180466
MeSH Terms: Animals, Dose Fractionation, Radiation, Humans, Proton Therapy, Radiometry, Radiotherapy Dosage
Show Abstract · Added March 30, 2020
Extraordinary normal tissue response to highly spatially fractionated X-ray beams has been explored for over 25 years. More recently, alternative radiation sources have been developed and utilized with the aim to evoke comparable effects. These include protons, which lend themselves well for this endeavour due to their physical depth dose characteristics as well as corresponding variable biological effectiveness. This paper addresses the motivation for using protons to generate spatially fractionated beams and reviews the technological implementations and experimental results to date. This includes simulation and feasibility studies, collimation and beam characteristics, dosimetry and biological considerations as well as the results of in vivo and in vitro studies. Experimental results are emerging indicating an extraordinary normal tissue sparing effect analogous to what has been observed for synchrotron generated X-ray microbeams. The potential for translational research and feasibility of spatially modulated proton beams in clinical settings is discussed.
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Secondary Malignancies in the Era of High-Precision Radiation Therapy.
Balcer-Kubiczek EK, Eley JG
(2018) Crit Rev Oncog 23: 93-112
MeSH Terms: Animals, Cell Transformation, Neoplastic, Humans, Neoplasms, Neoplasms, Second Primary, Precision Medicine, Radiation, Ionizing, Radiotherapy, Radiotherapy Dosage, Risk Assessment
Show Abstract · Added March 30, 2020
Although modern radiation therapy delivers a localized distribution of ionizing energy that can be used to cure primary cancers for many patients, the inevitable radiation exposure to non-targeted normal tissue leads to a risk of a radiation-related new cancer. Modern therapies often produce a complex spectrum of secondary particles, both charged and uncharged, that must be considered both in their physical radiation transport throughout the patient and their potential to induce biological damage, which depends on the microscopic energy deposition from the cascade of primary, secondary, and downstream particles. This work summarizes the experimental data for relative biological effectiveness for particles associated with modern radiotherapy in light of their capacity to induce secondary malignancies in patients. A distinction is highlighted between the radiobiological experimental data and the coarser metrics used frequently in radiation protection. For critical assessment of the risks of secondary malignancies for patients undergoing radiation therapy, a detailed description of primary and secondary radiation fields is needed, though not routinely considered for individual patient treatments. Furthermore, not only the particle type, but also the microscopic dose and track structure, must be considered, which points to a demand for detailed physics models and high-performance computing strategies to model the risks.
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Comparison of multi-institutional Varian ProBeam pencil beam scanning proton beam commissioning data.
Langner UW, Eley JG, Dong L, Langen K
(2017) J Appl Clin Med Phys 18: 96-107
MeSH Terms: Calibration, Proton Therapy, Radiometry, Radiotherapy Dosage, Reproducibility of Results
Show Abstract · Added March 30, 2020
PURPOSE - Commissioning beam data for proton spot scanning beams are compared for the first two Varian ProBeam sites in the United States, at the Maryland Proton Treatment Center (MPTC) and Scripps Proton Therapy Center (SPTC). In addition, the extent to which beams can be matched between gantry rooms at MPTC is investigated.
METHOD - Beam data for the two sites were acquired with independent dosimetry systems and compared. Integrated depth dose curves (IDDs) were acquired with Bragg peak ion chambers in a 3D water tank for pencil beams at both sites. Spot profiles were acquired at different distances from the isocenter at a gantry angle of 0° as well as a function of gantry angles. Absolute dose calibration was compared between SPTC and the gantries at MPTC. Dosimetric verification of test plans, output as a function of gantry angle, monitor unit (MU) linearity, end effects, dose rate dependence, and plan reproducibility were compared for different gantries at MPTC.
RESULTS - The IDDs for the two sites were similar, except in the plateau region, where the SPTC data were on average 4.5% higher for lower energies. This increase in the plateau region decreased as energy increased, with no marked difference for energies higher than 180 MeV. Range in water coincided for all energies within 0.5 mm. The sigmas of the spot profiles in air were within 10% agreement at isocenter. This difference increased as detector distance from the isocenter increased. Absolute doses for the gantries measured at both sites were within 1% agreement. Test plans, output as function of gantry angle, MU linearity, end effects, dose rate dependence, and plan reproducibility were all within tolerances given by TG142.
CONCLUSION - Beam data for the two sites and between different gantry rooms were well matched.
© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
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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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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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Outcomes of serial dilation for high-grade radiation-related esophageal strictures in head and neck cancer patients.
Francis DO, Hall E, Dang JH, Vlacich GR, Netterville JL, Vaezi MF
(2015) Laryngoscope 125: 856-62
MeSH Terms: Adult, Aged, Analysis of Variance, Carcinoma, Squamous Cell, Cohort Studies, Dilatation, Esophageal Stenosis, Esophagoscopy, Female, Follow-Up Studies, Head and Neck Neoplasms, Humans, Male, Middle Aged, Radiation Injuries, Radiotherapy Dosage, Recovery of Function, Retrospective Studies, Risk Assessment, Severity of Illness Index, Treatment Outcome
Show Abstract · Added September 28, 2015
OBJECTIVES/HYPOTHESIS - Dysphagia and esophageal stricture are frequent consequences of treatment for head and neck cancer. This study examines the effectiveness of the anterograde-retrograde rendezvous procedure and serial dilations in reestablishing esophageal patency to allow return to oral diet and gastrostomy tube removal in a cohort of patients with complete or near-complete esophageal stricture following nonsurgical cancer treatment.
STUDY DESIGN - Retrospective review of patients treated with radiation therapy with or without concurrent chemotherapy presented with complete or near-complete esophageal stricture. Patients underwent serial dilations using combined anterograde-retrograde dilation (rendezvous) techniques.
METHODS - Medical records of patients having undergone treatment between 2006 and 2012 were reviewed, and semistructured interviews were also conducted to determine current swallowing function and actual patient experience. The primary outcome was swallowing improvement that allowed for return to oral diet and/or gastrostomy tube removal. Outcomes were compared between patients with complete and near-complete (<5 mm in diameter) strictures and univariate analysis performed to identify associations between patient, cancer, and treatment characteristics on odds of gastrostomy tube removal.
RESULTS - Twenty-four patients (median age 59.5 years, 63% male, 91% Caucasian) underwent treatment. Fifty percent of patients had complete occlusion of the esophageal lumen. The majority of patients (92%) underwent either anterograde (54%) or combined antero-retrograde (38%) approach. Following a median (interquartile range) of 9 (6-20) dilation sessions, 42% of patients were able to return to an oral diet and/or had their gastrostomy tube removed. This outcome was independent of whether the stricture was complete or near complete (P = .67). Of patients who had their gastrostomy tubes removed, only 33.3% had ever smoked, compared to 92.3% of those whose tubes were not discharged (P = .007).
CONCLUSIONS - Recannulation is possible even in cases of complete or near-complete stricture. Several factors appear to impact the likelihood of successful outcome, but in this study, only patients with a history of smoking had a significantly lower likelihood of return to full oral diet.
© 2014 The American Laryngological, Rhinological and Otological Society, Inc.
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21 MeSH Terms
Dose to the inferior pharyngeal constrictor predicts prolonged gastrostomy tube dependence with concurrent intensity-modulated radiation therapy and chemotherapy for locally-advanced head and neck cancer.
Vlacich G, Spratt DE, Diaz R, Phillips JG, Crass J, Li CI, Shyr Y, Cmelak AJ
(2014) Radiother Oncol 110: 435-40
MeSH Terms: Adult, Aged, Aged, 80 and over, Chemoradiotherapy, Female, Gastrostomy, Head and Neck Neoplasms, Humans, Male, Middle Aged, Pharynx, Radiotherapy Dosage, Radiotherapy, Intensity-Modulated, Retrospective Studies
Show Abstract · Added March 10, 2014
BACKGROUND AND PURPOSE - To determine if dose and/or dose-volume parameters to anatomic swallowing structures are predictive of gastrostomy tube (PEG) dependence from chemotherapy-intensity modulated radiotherapy (IMRT) in locally advanced head and neck cancer (LAHNC).
METHODS AND MATERIALS - A retrospective study was performed on 141 consecutive patients with LAHNC (squamous cell) treated with definitive chemoIMRT with weekly concurrent carboplatin and paclitaxel. Late dysphagia was assessed by length of PEG requirement. Analysis of IMRT dose was retrospectively performed for critical swallowing structures.
RESULTS - Approximately 62% of patients required PEG, the majority placed during treatment. Mean and median time for PEG was 7.7 and 4.4 months respectively (range 1.4-43.8). Only IMRT dose to the inferior constrictor was significantly associated with length of PEG. Mean dose (of individual mean doses) was 47 Gy for prolonged PEG use versus 41 Gy for PEG ⩽ 12 months. V40 to the inferior constrictor also correlated with PEG >12 months (p = 0.02) with a mean V40 of 48% versus 41% for PEG ⩽ 12 months.
CONCLUSIONS - IMRT dose to the inferior constrictor correlated with persistent dysphagia requiring prolonged PEG use. Maintaining mean inferior constrictor dose to ⩽ 41 Gy and V40 to ⩽ 41% may help minimize gastrostomy tube dependence.
Copyright © 2014. Published by Elsevier Ireland Ltd.
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