WE-FG-BRB-00: The Challenges of Predicting RBE Effects in Particle Therapy and Opportunities for Improving Cancer Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Selective robust optimization: A new intensity-modulated proton therapy optimization strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yupeng; Niemela, Perttu; Siljamaki, Sami

2015-08-15

Purpose: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications. Methods: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy. The lung cancer cases had minimal tumor motion less than 5 mm, and, for the demonstration of the methodology,more » are assumed to be static. Results: Selective robust optimization achieved robust clinical target volume (CTV) coverage and at the same time increased nominal planning target volume coverage to 95.8%, compared to the 84.6% coverage achieved with CTV-based robust optimization in one of the lung cases. In the other lung case, the maximum dose in selective robust optimization was lowered from a dose of 131.3% in the CTV-based robust optimization to 113.6%. Selective robust optimization provided robust CTV coverage in the head and neck case, and at the same time improved controls over isodose distribution so that clinical requirements may be readily met. Conclusions: Selective robust optimization may provide the flexibility and capability necessary for meeting various clinical requirements in addition to achieving the required plan robustness in practical proton treatment planning settings.« less

Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview

PubMed Central

Weber, Damien C; Ares, Carmen; Lomax, Antony J; Kurtz, John M

2006-01-01

Postoperative radiation therapy substantially decreases local relapse and moderately reduces breast cancer mortality, but can be associated with increased late mortality due to cardiovascular morbidity and secondary malignancies. Sophistication of breast irradiation techniques, including conformal radiotherapy and intensity modulated radiation therapy, has been shown to markedly reduce cardiac and lung irradiation. The delivery of more conformal treatment can also be achieved with particle beam therapy using protons. Protons have superior dose distributional qualities compared to photons, as dose deposition occurs in a modulated narrow zone, called the Bragg peak. As a result, further dose optimization in breast cancer treatment can be reasonably expected with protons. In this review, we outline the potential indications and benefits of breast cancer radiotherapy with protons. Comparative planning studies and preliminary clinical data are detailed and future developments are considered. PMID:16857055

Spot-Scanning Proton Arc (SPArc) Therapy: The First Robust and Delivery-Efficient Spot-Scanning Proton Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Xuanfeng, E-mail: Xuanfeng.ding@beaumont.org; Li, Xiaoqiang; Zhang, J. Michele

Purpose: To present a novel robust and delivery-efficient spot-scanning proton arc (SPArc) therapy technique. Methods and Materials: A SPArc optimization algorithm was developed that integrates control point resampling, energy layer redistribution, energy layer filtration, and energy layer resampling. The feasibility of such a technique was evaluated using sample patients: 1 patient with locally advanced head and neck oropharyngeal cancer with bilateral lymph node coverage, and 1 with a nonmobile lung cancer. Plan quality, robustness, and total estimated delivery time were compared with the robust optimized multifield step-and-shoot arc plan without SPArc optimization (Arc{sub multi-field}) and the standard robust optimized intensity modulatedmore » proton therapy (IMPT) plan. Dose-volume histograms of target and organs at risk were analyzed, taking into account the setup and range uncertainties. Total delivery time was calculated on the basis of a 360° gantry room with 1 revolutions per minute gantry rotation speed, 2-millisecond spot switching time, 1-nA beam current, 0.01 minimum spot monitor unit, and energy layer switching time of 0.5 to 4 seconds. Results: The SPArc plan showed potential dosimetric advantages for both clinical sample cases. Compared with IMPT, SPArc delivered 8% and 14% less integral dose for oropharyngeal and lung cancer cases, respectively. Furthermore, evaluating the lung cancer plan compared with IMPT, it was evident that the maximum skin dose, the mean lung dose, and the maximum dose to ribs were reduced by 60%, 15%, and 35%, respectively, whereas the conformity index was improved from 7.6 (IMPT) to 4.0 (SPArc). The total treatment delivery time for lung and oropharyngeal cancer patients was reduced by 55% to 60% and 56% to 67%, respectively, when compared with Arc{sub multi-field} plans. Conclusion: The SPArc plan is the first robust and delivery-efficient proton spot-scanning arc therapy technique, which could potentially be implemented into routine clinical practice.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Camingue, Pamela; Christian, Rochelle; Ng, Davin

The purpose of this study was to compare 4 different external beam radiation therapy treatment techniques for the treatment of T1-2, N0, M0 glottic cancers: traditional lateral beams with wedges (3D), 5-field intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and proton therapy. Treatment plans in each technique were created for 10 patients using consistent planning parameters. The photon treatment plans were optimized using Philips Pinnacle{sub 3} v.9 and the IMRT and VMAT plans used the Direct Machine Parameter Optimization algorithm. The proton treatment plans were optimized using Varian Eclipse Proton v.8.9. The prescription used for each plan wasmore » 63 Gy in 28 fractions. The contours for spinal cord, right carotid artery, left carotid artery, and normal tissue were created with respect to the patient's bony anatomy so that proper comparisons of doses could be made with respect to volume. An example of the different isodose distributions will be shown. The data collection for comparison purposes includes: clinical treatment volume coverage, dose to spinal cord, dose to carotid arteries, and dose to normal tissue. Data comparisons will be displayed graphically showing the maximum, mean, median, and ranges of doses.« less

TH-CD-209-10: Scanning Proton Arc Therapy (SPArc) - The First Robust and Delivery-Efficient Spot Scanning Proton Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, X; Li, X; Zhang, J

Purpose: To develop a delivery-efficient proton spot-scanning arc therapy technique with robust plan quality. Methods: We developed a Scanning Proton Arc(SPArc) optimization algorithm integrated with (1)Control point re-sampling by splitting control point into adjacent sub-control points; (2)Energy layer re-distribution by assigning the original energy layers to the new sub-control points; (3)Energy layer filtration by deleting low MU weighting energy layers; (4)Energy layer re-sampling by sampling additional layers to ensure the optimal solution. A bilateral head and neck oropharynx case and a non-mobile lung target case were tested. Plan quality and total estimated delivery time were compared to original robust optimizedmore » multi-field step-and-shoot arc plan without SPArc optimization (Arcmulti-field) and standard robust optimized Intensity Modulated Proton Therapy(IMPT) plans. Dose-Volume-Histograms (DVH) of target and Organ-at-Risks (OARs) were analyzed along with all worst case scenarios. Total delivery time was calculated based on the assumption of a 360 degree gantry room with 1 RPM rotation speed, 2ms spot switching time, beam current 1nA, minimum spot weighting 0.01 MU, energy-layer-switching-time (ELST) from 0.5 to 4s. Results: Compared to IMPT, SPArc delivered less integral dose(−14% lung and −8% oropharynx). For lung case, SPArc reduced 60% of skin max dose, 35% of rib max dose and 15% of lung mean dose. Conformity Index is improved from 7.6(IMPT) to 4.0(SPArc). Compared to Arcmulti-field, SPArc reduced number of energy layers by 61%(276 layers in lung) and 80%(1008 layers in oropharynx) while kept the same robust plan quality. With ELST from 0.5s to 4s, it reduced 55%–60% of Arcmulti-field delivery time for the lung case and 56%–67% for the oropharynx case. Conclusion: SPArc is the first robust and delivery-efficient proton spot-scanning arc therapy technique which could be implemented in routine clinic. For modern proton machine with ELST close to 0.5s, SPArc would be a popular treatment option for both single and multi-room center.« less

A fast optimization algorithm for multicriteria intensity modulated proton therapy planning.

PubMed

Chen, Wei; Craft, David; Madden, Thomas M; Zhang, Kewu; Kooy, Hanne M; Herman, Gabor T

2010-09-01

To describe a fast projection algorithm for optimizing intensity modulated proton therapy (IMPT) plans and to describe and demonstrate the use of this algorithm in multicriteria IMPT planning. The authors develop a projection-based solver for a class of convex optimization problems and apply it to IMPT treatment planning. The speed of the solver permits its use in multicriteria optimization, where several optimizations are performed which span the space of possible treatment plans. The authors describe a plan database generation procedure which is customized to the requirements of the solver. The optimality precision of the solver can be specified by the user. The authors apply the algorithm to three clinical cases: A pancreas case, an esophagus case, and a tumor along the rib cage case. Detailed analysis of the pancreas case shows that the algorithm is orders of magnitude faster than industry-standard general purpose algorithms (MOSEK'S interior point optimizer, primal simplex optimizer, and dual simplex optimizer). Additionally, the projection solver has almost no memory overhead. The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.

WE-FG-BRB-02: Spatial Mapping of the RBE of Scanned Particle Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grosshans, D.

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Linear energy transfer incorporated intensity modulated proton therapy optimization

NASA Astrophysics Data System (ADS)

Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

2018-01-01

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.

A Dosimetric Comparison of Proton and Intensity-Modulated Photon Radiotherapy for Pediatric Parameningeal Rhabdomyosarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.

Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with atmore » least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.« less

Development of light ion therapy at the Karolinska Hospital and Institute.

PubMed

Svensson, Hans; Ringborg, Ulrik; Näslund, Ingemar; Brahme, Anders

2004-12-01

Recent developments in radiation therapy have made it possible to optimize the high dose region to cover almost any target volume and shape at the same time as the dose level to adjacent organs at risk is acceptable. Further implementations of IMRT (Intensity Modulated Radiation Therapy), and inverse treatment planning using already available technologies but also foreseeable improved design of therapy accelerators delivering electron- and photon beams, will bring these advances to the benefit of a broad population of cancer patients. Protons will therefore generally not be needed since in most situations the improvement will be insignificant or moderate due to the large lateral penumbra with deep proton therapy. A further step would be to use He-ions, which have only half the penumbra width of protons and still a fairly low-LET in the spread-out Bragg peak. There is however still a group of patients that cannot be helped by these advances as the tumor might be radioresistant for the presently utilized low ionization density beam qualities. The ultimate step in the therapy development process should therefore be to optimize the beam quality for each tumor-normal tissue situation. To facilitate beam quality optimization light ions are needed. It is argued that in many radioresistant tumors a dose-mean LET of 25-50 eV/nm in the target would be optimum as then tumor cells will be lost in the highest proportion through apoptotic cell kill and the superficial tissues will still be irradiated with a fairly low LET. Light ions using Li, Be, B, and C would then be the ideal choice. In this paper a light ion facility is outlined for the Karolinska University Hospital facilitating both dose distribution and beam quality optimization.

Clinical decision tool for optimal delivery of liver stereotactic body radiation therapy: Photons versus protons.

PubMed

Gandhi, Saumil J; Liang, Xing; Ding, Xuanfeng; Zhu, Timothy C; Ben-Josef, Edgar; Plastaras, John P; Metz, James M; Both, Stefan; Apisarnthanarax, Smith

2015-01-01

Stereotactic body radiation therapy (SBRT) for treatment of liver tumors is often limited by liver dose constraints. Protons offer potential for more liver sparing, but clinical situations in which protons may be superior to photons are not well described. We developed and validated a treatment decision model to determine whether liver tumors of certain sizes and locations are more suited for photon versus proton SBRT. Six spherical mock tumors from 1 to 6 cm in diameter were contoured on computed tomography images of 1 patient at 4 locations: dome, caudal, left medial, and central. Photon and proton plans were generated to deliver 50 Gy in 5 fractions to each tumor and optimized to deliver equivalent target coverage and maximal liver sparing. Using these plans, we developed a hypothesis-generating model to predict the optimal modality for maximal liver sparing based on tumor size and location. We then validated this model in 10 patients with liver tumors. Protons spared significantly more liver than photons for dome or central tumors ≥3 cm (dome: 134 ± 21 cm(3), P = .03; central: 108 ± 4 cm(3), P = .01). Our model correctly predicted the optimal SBRT modality for all 10 patients. For patients with dome or central tumors ≥3 cm, protons significantly increased the volume of liver spared (176 ± 21 cm(3), P = .01) and decreased the mean liver dose (8.4 vs 12.2 Gy, P = .01) while offering no significant advantage for tumors <3 cm at any location or for caudal and left medial tumors of any size. When feasible, protons should be considered as the radiation modality of choice for dome and central tumors >3 cm to allow maximal liver sparing and potentially reduce radiation toxicity. Protons should also be considered for any tumor >5 cm if photon plans fail to achieve adequate coverage or exceed the mean liver threshold. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

PubMed

Goddard, Lee C; Brodin, N Patrik; Bodner, William R; Garg, Madhur K; Tomé, Wolfgang A

2018-05-01

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Advances in knowledge: Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated.

Multifield optimization intensity modulated proton therapy for head and neck tumors: a translation to practice.

PubMed

Frank, Steven J; Cox, James D; Gillin, Michael; Mohan, Radhe; Garden, Adam S; Rosenthal, David I; Gunn, G Brandon; Weber, Randal S; Kies, Merrill S; Lewin, Jan S; Munsell, Mark F; Palmer, Matthew B; Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X Ronald

2014-07-15

We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment "spot by spot" and "layer by layer." Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials. Copyright © 2014 Elsevier Inc. All rights reserved.

Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stick, Line B., E-mail: line.bjerregaard.stick@regionh.dk; Niels Bohr Institute, Faculty of Science, University of Copenhagen, Copenhagen; Yu, Jen

Purpose: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby providing evidence-based estimates of the heterogeneity of treatment effects in consecutive cases for the 2 radiation treatment modalities. Methods and Materials: Forty-one patients referred for postlumpectomy comprehensive nodal photon irradiation for left-sided breast cancer were included. Comparative proton plans were optimized by a spot scanning technique with single-field optimization from 2 en face beams.more » Cardiotoxicity risk was estimated with the model of Darby et al, and risk of recurrence following a compromise of lymph node coverage was estimated by a linear dose-response model fitted to the recurrence data from the recently published EORTC (European Organisation for Research and Treatment of Cancer) 22922/10925 and NCIC-CTG (National Cancer Institute of Canada Clinical Trials Group) MA.20 randomized controlled trials. Results: Excess absolute risk of cardiac morbidity was small with photon therapy at an attained age of 80 years, with median values of 1.0% (range, 0.2%-2.9%) and 0.5% (range, 0.03%-1.0%) with and without cardiac risk factors, respectively, but even lower with proton therapy (0.13% [range, 0.02%-0.5%] and 0.06% [range, 0.004%-0.3%], respectively). The median estimated excess absolute risk of breast cancer recurrence after 10 years was 0.10% (range, 0.0%-0.9%) with photons and 0.02% (range, 0.0%-0.07%) with protons. The association between age of the patient and benefit from proton therapy was weak, almost non-existing (Spearman rank correlations of −0.15 and −0.30 with and without cardiac risk factors, respectively). Conclusions: Modern photon therapy yields limited risk of cardiac toxicity in most patients, but proton therapy can reduce the predicted risk of cardiac toxicity by up to 2.9% and the risk of breast cancer recurrence by 0.9% in individual patients. Predicted benefit correlates weakly with age. Combined assessment of the risk from cardiac exposure and inadequate target coverage is desirable for rational consideration of competing photon and proton therapy plans.« less

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 01: On the use of proton radiography to reduce beam range uncertainties and improve patient positioning accuracy in proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins-Fekete, Charles-Antoine; Beaulieu, Luc; Se

2016-08-15

To present two related developments of proton radiography (pRad) to minimize range uncertainty in proton therapy. The first combines a pRad with an X-ray CT to produce a patient-specific relative stopping power (RSP) map. The second aims to improve the pRad spatial resolution for accurate registration prior to the first. The enhanced-pRad can also be used in a novel proton-CT reconstruction algorithm. Monte Carlo pRad were computed from three phantoms; the Gammex, the Catphan and an anthropomorphic head. An optimized cubic-spline estimator derives the most likely path. The length crossed by the protons voxel-by-voxel was calculated by combining their estimatedmore » paths with the CT. The difference between the theoretical (length×RSP) and measured energy loss was minimized through a least squares optimization (LSO) algorithm yielding the RSP map. To increase pRad spatial resolution for registration with the CT, the phantom was discretized into voxels columns. The average column RSP was optimized to maximize the proton energy loss likelihood (MLE). Simulations showed precise RSP (<0.75%) for Gammex materials except low-density lung (<1.2%). For the head, accurate RSP were obtained (µ=−0.10%1.5σ=1.12%) and the range precision was improved (ΔR80 of −0.20±0.35%). Spatial resolution was increased in pRad (2.75 to 6.71 lp/cm) and pCT from MLE-enhanced pRad (2.83 to 5.86 lp/cm). The LSO decreases the range uncertainty (R80σ<1.0%) while the MLE-enhanced pRad spatial resolution (+244%) and is a great candidate for pCT reconstruction.« less

SU-E-T-266: Development of Evaluation System of Optimal Synchrotron Controlling Parameter for Spot Scanning Proton Therapy with Multiple Gate Irradiations in One Operation Cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamada, T; Fujii, Y; Hitachi Ltd., Hitachi-shi, Ibaraki

2015-06-15

Purpose: We have developed a gated spot scanning proton beam therapy system with real-time tumor-tracking. This system has the ability of multiple-gated irradiation in a single synchrotron operation cycle controlling the wait-time for consecutive gate signals during a flat-top phase so that the decrease in irradiation efficiency induced by irregular variation of gate signal is reduced. Our previous studies have shown that a 200 ms wait-time is appropriate to increase the average irradiation efficiency, but the optimal wait-time can vary patient by patient and day by day. In this research, we have developed an evaluation system of the optimal wait-timemore » in each irradiation based on the log data of the real-time-image gated proton beam therapy (RGPT) system. Methods: The developed system consists of logger for operation of RGPT system and software for evaluation of optimal wait-time. The logger records timing of gate on/off, timing and the dose of delivered beam spots, beam energy and timing of X-ray irradiation. The evaluation software calculates irradiation time in the case of different wait-time by simulating the multiple-gated irradiation operation using several timing information. Actual data preserved in the log data are used for gate on and off time, spot irradiation time, and time moving to the next spot. Design values are used for the acceleration and deceleration times. We applied this system to a patient treated with the RGPT system. Results: The evaluation system found the optimal wait-time of 390 ms that reduced the irradiation time by about 10 %. The irradiation time with actual wait-time used in treatment was reproduced with accuracy of 0.2 ms. Conclusion: For spot scanning proton therapy system with multiple-gated irradiation in one synchrotron operation cycle, an evaluation system of the optimal wait-time in each irradiation based on log data has been developed. Funding Support: Japan Society for the Promotion of Science (JSPS) through the FIRST Program.« less

Efficient monoenergetic proton beam from ultra-fast laser interaction with nanostructured targets

NASA Astrophysics Data System (ADS)

Fazeli, R.

2018-03-01

The broad energy spectrum of laser-accelerated proton beams is the most important difficulty associated with such particle sources on the way to future applications such as medical therapy, proton imaging, inertial fusion, and high-energy physics. The generation of proton beams with enhanced monoenergetic features through an ultra-intense laser interaction with optimized nanostructured targets is reported. Targets were irradiated by 40 fs laser pulses of intensity 5.5 ×1020 W c m -2 and wavelength 1 μm. The results of multi-parametric Particle-in-Cell calculations showed that proton beams with considerably reduced energy spread can be obtained by using the proposed nanostructured target. At optimized target dimensions, the proton spectrum was found to exhibit a narrow peak at about 63 MeV with a relative energy spread of ΔE /Epeak˜ 5 % which is efficiently lower than what is expected for unstructured double layer targets (˜70%).

TU-EF-304-07: Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y; UT Southwestern Medical Center, Dallas, TX; Tian, Z

2015-06-15

Purpose: Intensity-modulated proton therapy (IMPT) is increasingly used in proton therapy. For IMPT optimization, Monte Carlo (MC) is desired for spots dose calculations because of its high accuracy, especially in cases with a high level of heterogeneity. It is also preferred in biological optimization problems due to the capability of computing quantities related to biological effects. However, MC simulation is typically too slow to be used for this purpose. Although GPU-based MC engines have become available, the achieved efficiency is still not ideal. The purpose of this work is to develop a new optimization scheme to include GPU-based MC intomore » IMPT. Methods: A conventional approach using MC in IMPT simply calls the MC dose engine repeatedly for each spot dose calculations. However, this is not the optimal approach, because of the unnecessary computations on some spots that turned out to have very small weights after solving the optimization problem. GPU-memory writing conflict occurring at a small beam size also reduces computational efficiency. To solve these problems, we developed a new framework that iteratively performs MC dose calculations and plan optimizations. At each dose calculation step, the particles were sampled from different spots altogether with Metropolis algorithm, such that the particle number is proportional to the latest optimized spot intensity. Simultaneously transporting particles from multiple spots also mitigated the memory writing conflict problem. Results: We have validated the proposed MC-based optimization schemes in one prostate case. The total computation time of our method was ∼5–6 min on one NVIDIA GPU card, including both spot dose calculation and plan optimization, whereas a conventional method naively using the same GPU-based MC engine were ∼3 times slower. Conclusion: A fast GPU-based MC dose calculation method along with a novel optimization workflow is developed. The high efficiency makes it attractive for clinical usages.« less

SU-F-T-198: Dosimetric Comparison of Carbon and Proton Radiotherapy for Recurrent Nasopharynx Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheng, Y; Zhao, J; Wang, W

2016-06-15

Purpose: Various radiotherapy planning methods for locally recurrent nasopharynx carcinoma (R-NPC) have been proposed. The purpose of this study was to compare carbon and proton therapy for the treatment of R-NPC in terms of dose coverage for target volume and sparing for organs at risk (OARs). Methods: Six patients who were suffering from R-NPC and treated using carbon therapy were selected for this study. Treatment plans with a total dose of 57.5Gy (RBE) in 23 fractions were made using SIEMENS Syngo V11. An intensity-modulated radiotherapy optimization method was chosen for carbon plans (IMCT) while for proton plans both intensity-modulated radiotherapymore » (IMPT) and single beam optimization (proton-SBO) methods were chosen. Dose distributions, dose volume parameters, and selected dosimetric indices for target volumes and OARs were compared for all treatment plans. Results: All plans provided comparable PTV coverage. The volume covered by 95% of the prescribed dose was comparable for all three plans. The average values were 96.11%, 96.24% and 96.11% for IMCT, IMPT, and proton-SBO respectively. A significant reduction of the 80% and 50% dose volumes were observed for the IMCT plans compared to the IMPT and proton-SBO plans. Critical organs lateral to the target such as brain stem and spinal cord were better spared by IMPT than by proton-SBO, while IMCT spared those organs best. For organs in the beam path, such as parotid glands, the mean dose results were similar for all three plans. Conclusion: Carbon plans yielded better dose conformity than proton plans. They provided similar or better target coverage while significantly lowering the dose for normal tissues. Dose sparing for critical organs in IMPT plans was better than proton-SBO, however, IMPT is known to be more sensitive to range uncertainties. For proton plans it is essential to find a balance between the two optimization methods.« less

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans.

PubMed

Chaikh, Abdulhamid; Calugaru, Valentin; Bondiau, Pierre-Yves; Thariat, Juliette; Balosso, Jacques

2018-06-07

The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy. 14 pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value. Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < 0.05, using the three NTCP concepts. However, applying the same TD 50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better. treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Since estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD 50/5 , a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient's plan.

Accounting for range uncertainties in the optimization of intensity modulated proton therapy.

PubMed

Unkelbach, Jan; Chan, Timothy C Y; Bortfeld, Thomas

2007-05-21

Treatment plans optimized for intensity modulated proton therapy (IMPT) may be sensitive to range variations. The dose distribution may deteriorate substantially when the actual range of a pencil beam does not match the assumed range. We present two treatment planning concepts for IMPT which incorporate range uncertainties into the optimization. The first method is a probabilistic approach. The range of a pencil beam is assumed to be a random variable, which makes the delivered dose and the value of the objective function a random variable too. We then propose to optimize the expectation value of the objective function. The second approach is a robust formulation that applies methods developed in the field of robust linear programming. This approach optimizes the worst case dose distribution that may occur, assuming that the ranges of the pencil beams may vary within some interval. Both methods yield treatment plans that are considerably less sensitive to range variations compared to conventional treatment plans optimized without accounting for range uncertainties. In addition, both approaches--although conceptually different--yield very similar results on a qualitative level.

Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, Steven J., E-mail: sjfrank@mdanderson.org; Cox, James D.; Gillin, Michael

2014-07-15

Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effectmore » of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.« less

Strategic level proton therapy patient admission planning: a Markov decision process modeling approach.

PubMed

Gedik, Ridvan; Zhang, Shengfan; Rainwater, Chase

2017-06-01

A relatively new consideration in proton therapy planning is the requirement that the mix of patients treated from different categories satisfy desired mix percentages. Deviations from these percentages and their impacts on operational capabilities are of particular interest to healthcare planners. In this study, we investigate intelligent ways of admitting patients to a proton therapy facility that maximize the total expected number of treatment sessions (fractions) delivered to patients in a planning period with stochastic patient arrivals and penalize the deviation from the patient mix restrictions. We propose a Markov Decision Process (MDP) model that provides very useful insights in determining the best patient admission policies in the case of an unexpected opening in the facility (i.e., no-shows, appointment cancellations, etc.). In order to overcome the curse of dimensionality for larger and more realistic instances, we propose an aggregate MDP model that is able to approximate optimal patient admission policies using the worded weight aggregation technique. Our models are applicable to healthcare treatment facilities throughout the United States, but are motivated by collaboration with the University of Florida Proton Therapy Institute (UFPTI).

Improving proton therapy accessibility through seamless electronic integration of remote treatment planning sites.

PubMed

Belard, Arnaud; Dolney, Derek; Zelig, Tochner; McDonough, James; O'Connell, John

2011-06-01

Proton radiotherapy is a relatively scarce treatment modality in radiation oncology, with only nine centers currently operating in the United States. Funded by Public Law 107-248, the University of Pennsylvania and the Walter Reed Army Medical Center have developed a remote proton radiation therapy solution with the goals of improving access to proton radiation therapy for Department of Defense (DoD) beneficiaries while minimizing treatment delays and time spent away from home/work (time savings of up to 3 weeks per patient). To meet both Health Insurance Portability and Accountability Act guidelines and the more stringent security restrictions imposed by the DoD, our program developed a hybrid remote proton radiation therapy solution merging a CITRIX server with a JITIC-certified (Joint Interoperability Test Command) desktop videoconferencing unit. This conduit, thoroughly tested over a period of 6 months, integrates both institutions' radiation oncology treatment planning infrastructures into a single entity for DoD patients' treatment planning and delivery. This telemedicine solution enables DoD radiation oncologists and medical physicists the ability to (1) remotely access a proton therapy treatment planning platform, (2) transfer patient plans securely to the University of Pennsylvania patient database, and (3) initiate ad-hoc point-to-point and multipoint videoconferences to dynamically optimize and validate treatment plans. Our robust and secure remote treatment planning solution grants DoD patients not only access to a state-of-the-art treatment modality, but also participation in the treatment planning process by Walter Reed Army Medical Center radiation oncologists and medical physicists. This telemedicine system has the potential to lead to a greater integration of military treatment facilities and/or satellite clinics into regional proton therapy centers.

Fan-beam intensity modulated proton therapy.

PubMed

Hill, Patrick; Westerly, David; Mackie, Thomas

2013-11-01

This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems. Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of thismore » novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for small–tumor target patients. This optimizer will be used in an upcoming feasibility trial on LET{sub d} painting for radioresistant tumors.« less

Feasibility study of using statistical process control to customized quality assurance in proton therapy.

PubMed

Rah, Jeong-Eun; Shin, Dongho; Oh, Do Hoon; Kim, Tae Hyun; Kim, Gwe-Ya

2014-09-01

To evaluate and improve the reliability of proton quality assurance (QA) processes and, to provide an optimal customized tolerance level using the statistical process control (SPC) methodology. The authors investigated the consistency check of dose per monitor unit (D/MU) and range in proton beams to see whether it was within the tolerance level of the daily QA process. This study analyzed the difference between the measured and calculated ranges along the central axis to improve the patient-specific QA process in proton beams by using process capability indices. The authors established a customized tolerance level of ±2% for D/MU and ±0.5 mm for beam range in the daily proton QA process. In the authors' analysis of the process capability indices, the patient-specific range measurements were capable of a specification limit of ±2% in clinical plans. SPC methodology is a useful tool for customizing the optimal QA tolerance levels and improving the quality of proton machine maintenance, treatment delivery, and ultimately patient safety.

SU-F-T-178: Optimized Design of a Diamond Detector Specifically Dedicated to the Dose Distribution Measurements in Clinical Proton Pencil Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moignier, C; Pomorski, M; Agelou, M

2016-06-15

Purpose: In proton-therapy, pencil beam scanning (PBS) dosimetry presents a real challenge due to the small size of the beam (about 3 to 8 mm in FWHM), the pulsed high dose rate (up to 100 Gy/s) and the proton energy variation (about 30 MeV to 250 MeV). In the framework of French INSERM DEDIPRO project, a specifically dedicated single crystal diamond dosimeter (SCDDo) was developed with the objective of obtaining accurate measurements of the dose distribution in PBS modality. Methods: Monte Carlo simulations with MCNPX were performed. A small proton beam of 5 mm in FWHM was simulated as wellmore » as diamond devices with various size, thickness and holder composition. The calculated doses-to-diamond were compared with the doses-to-water in order to reduce the perturbation effects. Monte-Carlo simulations lead to an optimized SCDDo design for small proton beams dosimetry. Following the optimized design, SCDDos were mounted in water-equivalent holders with electrical connection adapted to standard electrometer. First, SCDDos performances (stability, repeatability, signal-to-background ratio…) were evaluated with conventional photon beams. Then, characterizations (dose linearity, dose rate dependence…) with wide proton beams were performed at proton-therapy center (IC-CPO) from Curie Institute (France) with the passive proton delivery technique, in order to confirm dosimetric requirements. Finally, depth-dose distributions were measured in a water tank, for native and modulated Bragg Peaks with the collimator of 12 cm, and compared to a commercial PPC05 parallel-plate ionization chamber reference detector. Lateral-dose profiles were also measured with the collimator of 5 mm, and compared to a commercial SFD diode. Results: The results show that SCDDo design does not disturb the dose distributions. Conclusion: The experimental dose distributions with the SCDDo are in good agreement with the commercial detectors and no energy dependence was observed with this device configuration.« less

SU-F-J-214: Dose Reduction by Spatially Optimized Image Quality Via Fluence Modulated Proton CT (FMpCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Angelis, L; Landry, G; Dedes, G

Purpose: Proton CT (pCT) is a promising imaging modality for reducing range uncertainty in image-guided proton therapy. Range uncertainties partially originate from X-ray CT number conversion to stopping power ratio (SPR) and are limiting the exploitation of the full potential of proton therapy. In this study we explore the concept of spatially dependent fluence modulated proton CT (FMpCT), for achieving optimal image quality in a clinical region of interest (ROI), while reducing significantly the imaging dose to the patient. Methods: The study was based on simulated ideal pCT using pencil beam (PB) scanning. A set of 250 MeV protons PBsmore » was used to create 360 projections of a cylindrical water phantom and a head and neck cancer patient. The tomographic images were reconstructed using a filtered backprojection (FBP) as well as an iterative algorithm (ITR). Different fluence modulation levels were investigated and their impact on the image was quantified in terms of SPR accuracy as well as noise within and outside selected ROIs, as a function of imaging dose. The unmodulated image served as reference. Results: Both FBP reconstruction and ITR without total variation (TV) yielded image quality in the ROIs similar to the reference images, for modulation down to 0.1 of the full proton fluence. The average dose was reduced by 75% for the water phantom and by 40% for the patient. FMpCT does not improve the noise for ITR with TV and modulation 0.1. Conclusion: This is the first work proposing and investigating FMpCT for producing optimal image quality for treatment planning and image guidance, while simultaneously reducing imaging dose. Future work will address spatial resolution effects and the impact of FMpCT on the quality of proton treatment plans for a prototype pCT scanner capable of list mode data acquisition. Acknowledgement: DFG-MAP DFG - Munich-Centre for Advanced Photonics (MAP)« less

A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.

PubMed

Ma, Jiasen; Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G

2014-12-01

Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. For relatively large and complex three-field head and neck cases, i.e., >100,000 spots with a target volume of ∼ 1000 cm(3) and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45,000 dollars. The fast calculation and optimization make the system easily expandable to robust and multicriteria optimization.

An end-to-end assessment of range uncertainty in proton therapy using animal tissues.

PubMed

Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

2016-11-21

Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams' superior dose advantage over conventional photon-based radiation therapy.

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grosshans, David R., E-mail: dgrossha@mdanderson.org; Zhu, X. Ronald; Melancon, Adam

2014-11-01

Purpose: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results: Tenmore » patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and with short-term follow-up, disease control rates and toxicity profiles were favorable.« less

Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery.

PubMed

Tommasino, Francesco; Durante, Marco; D'Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Farace, Paolo; Palma, Giuseppe; Schwarz, Marco; Cella, Laura; Pacelli, Roberto

2017-05-01

Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database. Intensity modulated photon (IMRT) and IMPT plans were calculated with iso-tumor-coverage criteria and according to RTOG 1005 guidelines. Proton plans were computed with and without skin optimization. Published NTCP models were employed to estimate the risk of different toxicity endpoints for skin, lung, heart and its substructures. Acute skin NTCP evaluation suggests a lower toxicity level with IMPT compared to IMRT when the skin is included in proton optimization strategy (0.1% versus 1.7%, p < 0.001). Dosimetric results show that, with the same level of tumor coverage, IMPT attains significant heart and lung dose sparing compared with IMRT. By NTCP model-based analysis, an overall reduction in the cardiopulmonary toxicity risk prediction can be observed for all IMPT compared to IMRT plans: the relative risk reduction from protons varies between 0.1 and 0.7 depending on the considered toxicity endpoint. Our analysis suggests that IMPT might be safely applied without increasing the risk of severe acute radiation induced skin toxicity. The quantitative risk estimates also support the potential clinical benefits of IMPT for left-side BC irradiation due to lower risk of cardiac and pulmonary morbidity. The applied approach might be relevant on the long term for the setup of cost-effectiveness evaluation strategies based on NTCP predictions.

SU-E-T-214: Intensity Modulated Proton Therapy (IMPT) Based On Passively Scattered Protons and Multi-Leaf Collimation: Prototype TPS and Dosimetry Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez-Parcerisa, D; Carabe-Fernandez, A

2014-06-01

Purpose. Intensity-modulated proton therapy is usually implemented with multi-field optimization of pencil-beam scanning (PBS) proton fields. However, at the view of the experience with photon-IMRT, proton facilities equipped with double-scattering (DS) delivery and multi-leaf collimation (MLC) could produce highly conformal dose distributions (and possibly eliminate the need for patient-specific compensators) with a clever use of their MLC field shaping, provided that an optimal inverse TPS is developed. Methods. A prototype TPS was developed in MATLAB. The dose calculation process was based on a fluence-dose algorithm on an adaptive divergent grid. A database of dose kernels was precalculated in order tomore » allow for fast variations of the field range and modulation during optimization. The inverse planning process was based on the adaptive simulated annealing approach, with direct aperture optimization of the MLC leaves. A dosimetry study was performed on a phantom formed by three concentrical semicylinders separated by 5 mm, of which the inner-most and outer-most were regarded as organs at risk (OARs), and the middle one as the PTV. We chose a concave target (which is not treatable with conventional DS fields) to show the potential of our technique. The optimizer was configured to minimize the mean dose to the OARs while keeping a good coverage of the target. Results. The plan produced by the prototype TPS achieved a conformity index of 1.34, with the mean doses to the OARs below 78% of the prescribed dose. This Result is hardly achievable with traditional conformal DS technique with compensators, and it compares to what can be obtained with PBS. Conclusion. It is certainly feasible to produce IMPT fields with MLC passive scattering fields. With a fully developed treatment planning system, the produced plans can be superior to traditional DS plans in terms of plan conformity and dose to organs at risk.« less

The management of gastro-oesophageal reflux disease.

PubMed

Keung, Charlotte; Hebbard, Geoffrey

2016-02-01

If there are no features of serious disease, suspected gastro-oesophageal reflux disease can be initially managed with a trial of a proton pump inhibitor for 4-8 weeks. This should be taken 30-60 minutes before food for optimal effect. Once symptoms are controlled, attempt to withdraw acid suppression therapy. If symptoms recur, use the minimum dose that controls symptoms. Patients who have severe erosive oesophagitis, scleroderma oesophagus or Barrett's oesophagus require long-term treatment with a proton pump inhibitor. Lifestyle modification strategies can help gastro-oesophageal reflux disease. Weight loss has the strongest evidence for efficacy. Further investigation and a specialist referral are required if there is no response to proton pump inhibitor therapy. Atypical symptoms or signs of serious disease also need investigation.

SU-E-T-109: An Investigation of Including Variable Relative Biological Effectiveness in Intensity Modulated Proton Therapy Planning Optimization for Head and Neck Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, W; Zaghian, M; Lim, G

2015-06-15

Purpose: The current practice of considering the relative biological effectiveness (RBE) of protons in intensity modulated proton therapy (IMPT) planning is to use a generic RBE value of 1.1. However, RBE is indeed a variable depending on the dose per fraction, the linear energy transfer, tissue parameters, etc. In this study, we investigate the impact of using variable RBE based optimization (vRBE-OPT) on IMPT dose distributions compared by conventional fixed RBE based optimization (fRBE-OPT). Methods: Proton plans of three head and neck cancer patients were included for our study. In order to calculate variable RBE, tissue specific parameters were obtainedmore » from the literature and dose averaged LET values were calculated by Monte Carlo simulations. Biological effects were calculated using the linear quadratic model and they were utilized in the variable RBE based optimization. We used a Polak-Ribiere conjugate gradient algorithm to solve the model. In fixed RBE based optimization, we used conventional physical dose optimization to optimize doses weighted by 1.1. IMPT plans for each patient were optimized by both methods (vRBE-OPT and fRBE-OPT). Both variable and fixed RBE weighted dose distributions were calculated for both methods and compared by dosimetric measures. Results: The variable RBE weighted dose distributions were more homogenous within the targets, compared with the fixed RBE weighted dose distributions for the plans created by vRBE-OPT. We observed that there were noticeable deviations between variable and fixed RBE weighted dose distributions if the plan were optimized by fRBE-OPT. For organs at risk sparing, dose distributions from both methods were comparable. Conclusion: Biological dose based optimization rather than conventional physical dose based optimization in IMPT planning may bring benefit in improved tumor control when evaluating biologically equivalent dose, without sacrificing OAR sparing, for head and neck cancer patients. The research is supported in part by National Institutes of Health Grant No. 2U19CA021239-35.« less

Inclusion of a variable RBE into proton and photon plan comparison for various fractionation schedules in prostate radiation therapy.

PubMed

Ödén, Jakob; Eriksson, Kjell; Toma-Dasu, Iuliana

2017-03-01

A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction, and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions. Photon and proton dose plans were created for three generic prostate cancer cases. Three BED 3Gy equivalent schedules were studied, 78, 57.2, and 42.8 Gy in 39, 15, and 7 fractions, respectively. The proton plans were optimized assuming a constant RBE of 1.1. By using the Monte Carlo calculated dose-averaged LET (LET d ) distribution and assuming α/β values on voxel level, three variable RBE models were applied to the proton dose plans. The impact of the variable RBE was studied in the plan comparison, which was based on the dose distribution, DVHs, and normal tissue complication probabilities (NTCP) for the rectum. Subsequently, the physical proton dose was reoptimized for each proton plan based on the LET d distribution, to achieve a homogeneous RBE-weighted target dose when applying a specific RBE model and still fulfill the clinical goals for the rectum and bladder. All the photon and proton plans assuming RBE = 1.1 met the clinical goals with similar target coverage. The proton plans fulfilled the robustness criteria in terms of range and setup uncertainty. Applying the variable RBE models generally resulted in higher target doses and rectum NTCP compared to the photon plans. The increase was most pronounced for the fractionation dose of 2 Gy(RBE), whereas it was of less magnitude and more dependent on model and α/β assumption for the hypofractionated schedules. The reoptimized proton plans proved to be robust and showed similar target coverage and doses to the organs at risk as the proton plans optimized with a constant RBE. Model predicted RBE values may differ substantially from 1.1. This is most pronounced for fractionation doses of around 2 Gy(RBE) with higher doses to the target and the OARs, whereas the effect seems to be of less importance for the hypofractionated schedules. This could result in misleading conclusions when comparing proton plans to photon plans. By accounting for a variable RBE in the optimization process, robust and clinically acceptable dose plans, with the potential of lowering rectal NTCP, may be generated by reoptimizing the physical dose. However, the direction and magnitude of the changes in the physical proton dose to the prostate are dependent on RBE model and α/β assumptions and should therefore be used conservatively. © 2017 American Association of Physicists in Medicine.

SU-D-BRC-01: An Automatic Beam Model Commissioning Method for Monte Carlo Simulations in Pencil-Beam Scanning Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, N; Shen, C; Tian, Z

Purpose: Monte Carlo (MC) simulation is typically regarded as the most accurate dose calculation method for proton therapy. Yet for real clinical cases, the overall accuracy also depends on that of the MC beam model. Commissioning a beam model to faithfully represent a real beam requires finely tuning a set of model parameters, which could be tedious given the large number of pencil beams to commmission. This abstract reports an automatic beam-model commissioning method for pencil-beam scanning proton therapy via an optimization approach. Methods: We modeled a real pencil beam with energy and spatial spread following Gaussian distributions. Mean energy,more » and energy and spatial spread are model parameters. To commission against a real beam, we first performed MC simulations to calculate dose distributions of a set of ideal (monoenergetic, zero-size) pencil beams. Dose distribution for a real pencil beam is hence linear superposition of doses for those ideal pencil beams with weights in the Gaussian form. We formulated the commissioning task as an optimization problem, such that the calculated central axis depth dose and lateral profiles at several depths match corresponding measurements. An iterative algorithm combining conjugate gradient method and parameter fitting was employed to solve the optimization problem. We validated our method in simulation studies. Results: We calculated dose distributions for three real pencil beams with nominal energies 83, 147 and 199 MeV using realistic beam parameters. These data were regarded as measurements and used for commission. After commissioning, average difference in energy and beam spread between determined values and ground truth were 4.6% and 0.2%. With the commissioned model, we recomputed dose. Mean dose differences from measurements were 0.64%, 0.20% and 0.25%. Conclusion: The developed automatic MC beam-model commissioning method for pencil-beam scanning proton therapy can determine beam model parameters with satisfactory accuracy.« less

SU-D-BRC-02: Application of Six Sigma Approach to Improve the Efficiency of Patient-Specific QA in Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

LAH, J; Shin, D; Manger, R

Purpose: To show how the Six Sigma DMAIC (Define-Measure-Analyze-Improve-Control) can be used for improving and optimizing the efficiency of patient-specific QA process by designing site-specific range tolerances. Methods: The Six Sigma tools (process flow diagram, cause and effect, capability analysis, Pareto chart, and control chart) were utilized to determine the steps that need focus for improving the patient-specific QA process. The patient-specific range QA plans were selected according to 7 treatment site groups, a total of 1437 cases. The process capability index, Cpm was used to guide the tolerance design of patient site-specific range. We also analyzed the financial impactmore » of this project. Results: Our results suggested that the patient range measurements were non-capable at the current tolerance level of ±1 mm in clinical proton plans. The optimized tolerances were calculated for treatment sites. Control charts for the patient QA time were constructed to compare QA time before and after the new tolerances were implemented. It is found that overall processing time was decreased by 24.3% after establishing new site-specific range tolerances. The QA failure for whole process in proton therapy would lead up to a 46% increase in total cost. This result can also predict how costs are affected by changes in adopting the tolerance design. Conclusion: We often believe that the quality and performance of proton therapy can easily be improved by merely tightening some or all of its tolerance requirements. This can become costly, however, and it is not necessarily a guarantee of better performance. The tolerance design is not a task to be undertaken without careful thought. The Six Sigma DMAIC can be used to improve the QA process by setting optimized tolerances. When tolerance design is optimized, the quality is reasonably balanced with time and cost demands.« less

Impact of spot size on plan quality of spot scanning proton radiosurgery for peripheral brain lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Dongxu, E-mail: dongxu-wang@uiowa.edu; Dirksen, Blake; Hyer, Daniel E.

Purpose: To determine the plan quality of proton spot scanning (SS) radiosurgery as a function of spot size (in-air sigma) in comparison to x-ray radiosurgery for treating peripheral brain lesions. Methods: Single-field optimized (SFO) proton SS plans with sigma ranging from 1 to 8 mm, cone-based x-ray radiosurgery (Cone), and x-ray volumetric modulated arc therapy (VMAT) plans were generated for 11 patients. Plans were evaluated using secondary cancer risk and brain necrosis normal tissue complication probability (NTCP). Results: For all patients, secondary cancer is a negligible risk compared to brain necrosis NTCP. Secondary cancer risk was lower in proton SSmore » plans than in photon plans regardless of spot size (p = 0.001). Brain necrosis NTCP increased monotonically from an average of 2.34/100 (range 0.42/100–4.49/100) to 6.05/100 (range 1.38/100–11.6/100) as sigma increased from 1 to 8 mm, compared to the average of 6.01/100 (range 0.82/100–11.5/100) for Cone and 5.22/100 (range 1.37/100–8.00/100) for VMAT. An in-air sigma less than 4.3 mm was required for proton SS plans to reduce NTCP over photon techniques for the cohort of patients studied with statistical significance (p = 0.0186). Proton SS plans with in-air sigma larger than 7.1 mm had significantly greater brain necrosis NTCP than photon techniques (p = 0.0322). Conclusions: For treating peripheral brain lesions—where proton therapy would be expected to have the greatest depth-dose advantage over photon therapy—the lateral penumbra strongly impacts the SS plan quality relative to photon techniques: proton beamlet sigma at patient surface must be small (<7.1 mm for three-beam single-field optimized SS plans) in order to achieve comparable or smaller brain necrosis NTCP relative to photon radiosurgery techniques. Achieving such small in-air sigma values at low energy (<70 MeV) is a major technological challenge in commercially available proton therapy systems.« less

Falcon: automated optimization method for arbitrary assessment criteria

DOEpatents

Yang, Tser-Yuan; Moses, Edward I.; Hartmann-Siantar, Christine

2001-01-01

FALCON is a method for automatic multivariable optimization for arbitrary assessment criteria that can be applied to numerous fields where outcome simulation is combined with optimization and assessment criteria. A specific implementation of FALCON is for automatic radiation therapy treatment planning. In this application, FALCON implements dose calculations into the planning process and optimizes available beam delivery modifier parameters to determine the treatment plan that best meets clinical decision-making criteria. FALCON is described in the context of the optimization of external-beam radiation therapy and intensity modulated radiation therapy (IMRT), but the concepts could also be applied to internal (brachytherapy) radiotherapy. The radiation beams could consist of photons or any charged or uncharged particles. The concept of optimizing source distributions can be applied to complex radiography (e.g. flash x-ray or proton) to improve the imaging capabilities of facilities proposed for science-based stockpile stewardship.

Conception of a New Recoil Proton Telescope for Real-Time Neutron Spectrometry in Proton-Therapy

NASA Astrophysics Data System (ADS)

Combe, Rodolphe; Arbor, Nicolas; el Bitar, Ziad; Higueret, Stéphane; Husson, Daniel

2018-01-01

Neutrons are the main type of secondary particles emitted in proton-therapy. Because of the risk of secondary cancer and other late occurring effects, the neutron dose should be included in the out-of-field dose calculations. A neutron spectrometer has to be used to take into account the energy dependence of the neutron radiological weighting factor. Due to its high dependence on various parameters of the irradiation (beam, accelerator, patient), the neutron spectrum should be measured independently for each treatment. The current reference method for the measurement of the neutron energy, the Bonner Sphere System, consists of several homogeneous polyethylene spheres with increasing diameters equipped with a proportional counter. It provides a highresolution reconstruction of the neutron spectrum but requires a time-consuming work of signal deconvolution. New neutron spectrometers are being developed, but the main experimental limitation remains the high neutron flux in proton therapy treatment rooms. A new model of a real-time neutron spectrometer, based on a Recoil Proton Telescope technology, has been developed at the IPHC. It enables a real-time high-rate reconstruction of the neutron spectrum from the measurement of the recoil proton trajectory and energy. A new fast-readout microelectronic integrated sensor, called FastPixN, has been developed for this specific purpose. A first prototype, able to detect neutrons between 5 and 20 MeV, has already been validated for metrology with the AMANDE facility at Cadarache. The geometry of the new Recoil Proton Telescope has been optimized via extensive Geant4 Monte Carlo simulations. Uncertainty sources have been carefully studied in order to improve simultaneously efficiency and energy resolution, and solutions have been found to suppress the various expected backgrounds. We are currently upgrading the prototype for secondary neutron detection in proton therapy applications.

Feasibility study of using statistical process control to customized quality assurance in proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rah, Jeong-Eun; Oh, Do Hoon; Shin, Dongho

Purpose: To evaluate and improve the reliability of proton quality assurance (QA) processes and, to provide an optimal customized tolerance level using the statistical process control (SPC) methodology. Methods: The authors investigated the consistency check of dose per monitor unit (D/MU) and range in proton beams to see whether it was within the tolerance level of the daily QA process. This study analyzed the difference between the measured and calculated ranges along the central axis to improve the patient-specific QA process in proton beams by using process capability indices. Results: The authors established a customized tolerance level of ±2% formore » D/MU and ±0.5 mm for beam range in the daily proton QA process. In the authors’ analysis of the process capability indices, the patient-specific range measurements were capable of a specification limit of ±2% in clinical plans. Conclusions: SPC methodology is a useful tool for customizing the optimal QA tolerance levels and improving the quality of proton machine maintenance, treatment delivery, and ultimately patient safety.« less

Nanodosimetry-Based Plan Optimization for Particle Therapy

PubMed Central

Schulte, Reinhard W.

2015-01-01

Treatment planning for particle therapy is currently an active field of research due uncertainty in how to modify physical dose in order to create a uniform biological dose response in the target. A novel treatment plan optimization strategy based on measurable nanodosimetric quantities rather than biophysical models is proposed in this work. Simplified proton and carbon treatment plans were simulated in a water phantom to investigate the optimization feasibility. Track structures of the mixed radiation field produced at different depths in the target volume were simulated with Geant4-DNA and nanodosimetric descriptors were calculated. The fluences of the treatment field pencil beams were optimized in order to create a mixed field with equal nanodosimetric descriptors at each of the multiple positions in spread-out particle Bragg peaks. For both proton and carbon ion plans, a uniform spatial distribution of nanodosimetric descriptors could be obtained by optimizing opposing-field but not single-field plans. The results obtained indicate that uniform nanodosimetrically weighted plans, which may also be radiobiologically uniform, can be obtained with this approach. Future investigations need to demonstrate that this approach is also feasible for more complicated beam arrangements and that it leads to biologically uniform response in tumor cells and tissues. PMID:26167202

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Samantha, E-mail: samantha.warren@oncology.ox.ac.uk; Partridge, Mike; Bolsi, Alessandra

Purpose: Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods andmore » Materials: For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV){sub 50Gy} or PTV{sub 62.5Gy} (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results: SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D{sub 98} was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D{sub 98} was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D{sub 98} was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D{sub 98} was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions: The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial.« less

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

PubMed Central

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J.; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

2016-01-01

Purpose Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods and Materials For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. PMID:27084641

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning.

PubMed

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A

2016-05-01

Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose-volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The management of gastro-oesophageal reflux disease

PubMed Central

Keung, Charlotte; Hebbard, Geoffrey

2016-01-01

SUMMARY If there are no features of serious disease, suspected gastro-oesophageal reflux disease can be initially managed with a trial of a proton pump inhibitor for 4–8 weeks. This should be taken 30–60 minutes before food for optimal effect. Once symptoms are controlled, attempt to withdraw acid suppression therapy. If symptoms recur, use the minimum dose that controls symptoms. Patients who have severe erosive oesophagitis, scleroderma oesophagus or Barrett’s oesophagus require long-term treatment with a proton pump inhibitor. Lifestyle modification strategies can help gastro-oesophageal reflux disease. Weight loss has the strongest evidence for efficacy. Further investigation and a specialist referral are required if there is no response to proton pump inhibitor therapy. Atypical symptoms or signs of serious disease also need investigation. PMID:27041798

The proton therapy nozzles at Samsung Medical Center: A Monte Carlo simulation study using TOPAS

NASA Astrophysics Data System (ADS)

Chung, Kwangzoo; Kim, Jinsung; Kim, Dae-Hyun; Ahn, Sunghwan; Han, Youngyih

2015-07-01

To expedite the commissioning process of the proton therapy system at Samsung Medical Center (SMC), we have developed a Monte Carlo simulation model of the proton therapy nozzles by using TOol for PArticle Simulation (TOPAS). At SMC proton therapy center, we have two gantry rooms with different types of nozzles: a multi-purpose nozzle and a dedicated scanning nozzle. Each nozzle has been modeled in detail following the geometry information provided by the manufacturer, Sumitomo Heavy Industries, Ltd. For this purpose, the novel features of TOPAS, such as the time feature or the ridge filter class, have been used, and the appropriate physics models for proton nozzle simulation have been defined. Dosimetric properties, like percent depth dose curve, spreadout Bragg peak (SOBP), and beam spot size, have been simulated and verified against measured beam data. Beyond the Monte Carlo nozzle modeling, we have developed an interface between TOPAS and the treatment planning system (TPS), RayStation. An exported radiotherapy (RT) plan from the TPS is interpreted by using an interface and is then translated into the TOPAS input text. The developed Monte Carlo nozzle model can be used to estimate the non-beam performance, such as the neutron background, of the nozzles. Furthermore, the nozzle model can be used to study the mechanical optimization of the design of the nozzle.

Fast multipurpose Monte Carlo simulation for proton therapy using multi- and many-core CPU architectures.

PubMed

Souris, Kevin; Lee, John Aldo; Sterpin, Edmond

2016-04-01

Accuracy in proton therapy treatment planning can be improved using Monte Carlo (MC) simulations. However the long computation time of such methods hinders their use in clinical routine. This work aims to develop a fast multipurpose Monte Carlo simulation tool for proton therapy using massively parallel central processing unit (CPU) architectures. A new Monte Carlo, called MCsquare (many-core Monte Carlo), has been designed and optimized for the last generation of Intel Xeon processors and Intel Xeon Phi coprocessors. These massively parallel architectures offer the flexibility and the computational power suitable to MC methods. The class-II condensed history algorithm of MCsquare provides a fast and yet accurate method of simulating heavy charged particles such as protons, deuterons, and alphas inside voxelized geometries. Hard ionizations, with energy losses above a user-specified threshold, are simulated individually while soft events are regrouped in a multiple scattering theory. Elastic and inelastic nuclear interactions are sampled from ICRU 63 differential cross sections, thereby allowing for the computation of prompt gamma emission profiles. MCsquare has been benchmarked with the gate/geant4 Monte Carlo application for homogeneous and heterogeneous geometries. Comparisons with gate/geant4 for various geometries show deviations within 2%-1 mm. In spite of the limited memory bandwidth of the coprocessor simulation time is below 25 s for 10(7) primary 200 MeV protons in average soft tissues using all Xeon Phi and CPU resources embedded in a single desktop unit. MCsquare exploits the flexibility of CPU architectures to provide a multipurpose MC simulation tool. Optimized code enables the use of accurate MC calculation within a reasonable computation time, adequate for clinical practice. MCsquare also simulates prompt gamma emission and can thus be used also for in vivo range verification.

SU-E-T-529: Is MFO-IMPT Robust Enough for the Treatment of Head and Neck Tumors? A 2-Year Outcome Analysis Following Proton Therapy On the First 50 Oropharynx Patients at the MD Anderson Cancer Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, S; Garden, A; Anderson, M

Purpose: Multi-field optimization intensity modulated proton therapy (MFO-IMPT) for oropharyngeal tumors has been established using robust planning, robust analysis, and robust optimization techniques. While there are inherent uncertainties in proton therapy treatment planning and delivery, outcome reporting are important to validate the proton treatment process. The purpose of this study is to report the first 50 oropharyngeal tumor patients treated de-novo at a single institution with MFO-IMPT. Methods: The data from the first 50 patients with squamous cell carcinoma of the oropharynx treated at MD Anderson Cancer Center from January 2011 to December 2014 on a prospective IRB approved protocolmore » were analyzed. Outcomes were analyzed to include local, regional, and distant treatment failures. Acute and late toxicities were analyzed by CTCAE v4.0. Results: All patients were treated with definitive intent. The median follow-up time of the 50 patients was 25 months. Patients by gender were male (84%) and female (16%). The average age was 61 years. 50% of patients were never smokers and 4% were current smokers. Presentation by stage; I–1, II–0, III– 9, IVA–37 (74%), IVB–3. 88% of patients were HPV/p16+. Patients were treated to 66–70 CGE. One local failure was reported at 13 months following treatment. One neck failure was reported at 12 months. 94% of patients were alive with no evidence of disease. One patient died without evidence of disease. There were no Grade 4 or Grade 5 toxicities. Conclusion: MFO-IMPT for oropharyngeal tumors is robust and provides excellent outcomes 2 years after treatment. A randomized trial is underway to determine if proton therapy will reduce chronic late toxicities of IMRT.« less

SU-FF-T-668: A Simple Algorithm for Range Modulation Wheel Design in Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nie, X; Nazaryan, Vahagn; Gueye, Paul

2009-06-01

Purpose: To develop a simple algorithm in designing the range modulation wheel to generate a very smooth Spread-Out Bragg peak (SOBP) for proton therapy.Method and Materials: A simple algorithm has been developed to generate the weight factors in corresponding pristine Bragg peaks which composed a smooth SOBP in proton therapy. We used a modified analytical Bragg peak function based on Monte Carol simulation tool-kits of Geant4 as pristine Bragg peaks input in our algorithm. A simple METLAB(R) Quad Program was introduced to optimize the cost function in our algorithm. Results: We found out that the existed analytical function of Braggmore » peak can't directly use as pristine Bragg peak dose-depth profile input file in optimization of the weight factors since this model didn't take into account of the scattering factors introducing from the range shifts in modifying the proton beam energies. We have done Geant4 simulations for proton energy of 63.4 MeV with a 1.08 cm SOBP for variation of pristine Bragg peaks which composed this SOBP and modified the existed analytical Bragg peak functions for their peak heights, ranges of R{sub 0}, and Gaussian energies {sigma}{sub E}. We found out that 19 pristine Bragg peaks are enough to achieve a flatness of 1.5% of SOBP which is the best flatness in the publications. Conclusion: This work develops a simple algorithm to generate the weight factors which is used to design a range modulation wheel to generate a smooth SOBP in protonradiation therapy. We have found out that a medium number of pristine Bragg peaks are enough to generate a SOBP with flatness less than 2%. It is potential to generate data base to store in the treatment plan to produce a clinic acceptable SOBP by using our simple algorithm.« less

SU-F-J-57: Effectiveness of Daily CT-Based Three-Dimensional Image Guided and Adaptive Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moriya, S; National Cancer Center, Kashiwa, Chiba; Tachibana, H

Purpose: Daily CT-based three-dimensional image-guided and adaptive (CTIGRT-ART) proton therapy system was designed and developed. We also evaluated the effectiveness of the CTIGRT-ART. Methods: Retrospective analysis was performed in three lung cancer patients: Proton treatment planning was performed using CT image datasets acquired by Toshiba Aquilion ONE. Planning target volume and surrounding organs were contoured by a well-trained radiation oncologist. Dose distribution was optimized using 180-deg. and 270-deg. two fields in passive scattering proton therapy. Well commissioned Simplified Monte Carlo algorithm was used as dose calculation engine. Daily consecutive CT image datasets was acquired by an in-room CT (Toshiba Aquilionmore » LB). In our in-house program, two image registrations for bone and tumor were performed to shift the isocenter using treatment CT image dataset. Subsequently, dose recalculation was performed after the shift of the isocenter. When the dose distribution after the tumor registration exhibits change of dosimetric parameter of CTV D90% compared to the initial plan, an additional process of was performed that the range shifter thickness was optimized. Dose distribution with CTV D90% for the bone registration, the tumor registration only and adaptive plan with the tumor registration was compared to the initial plan. Results: In the bone registration, tumor dose coverage was decreased by 16% on average (Maximum: 56%). The tumor registration shows better coverage than the bone registration, however the coverage was also decreased by 9% (Maximum: 22%) The adaptive plan shows similar dose coverage of the tumor (Average: 2%, Maximum: 7%). Conclusion: There is a high possibility that only image registration for bone and tumor may reduce tumor coverage. Thus, our proposed methodology of image guidance and adaptive planning using the range adaptation after tumor registration would be effective for proton therapy. This research is partially supported by Japan Agency for Medical Research and Development (AMED).« less

Optimization and verification of image reconstruction for a Compton camera towards application as an on-line monitor for particle therapy

NASA Astrophysics Data System (ADS)

Taya, T.; Kataoka, J.; Kishimoto, A.; Tagawa, L.; Mochizuki, S.; Toshito, T.; Kimura, M.; Nagao, Y.; Kurita, K.; Yamaguchi, M.; Kawachi, N.

2017-07-01

Particle therapy is an advanced cancer therapy that uses a feature known as the Bragg peak, in which particle beams suddenly lose their energy near the end of their range. The Bragg peak enables particle beams to damage tumors effectively. To achieve precise therapy, the demand for accurate and quantitative imaging of the beam irradiation region or dosage during therapy has increased. The most common method of particle range verification is imaging of annihilation gamma rays by positron emission tomography. Not only 511-keV gamma rays but also prompt gamma rays are generated during therapy; therefore, the Compton camera is expected to be used as an on-line monitor for particle therapy, as it can image these gamma rays in real time. Proton therapy, one of the most common particle therapies, uses a proton beam of approximately 200 MeV, which has a range of ~ 25 cm in water. As gamma rays are emitted along the path of the proton beam, quantitative evaluation of the reconstructed images of diffuse sources becomes crucial, but it is far from being fully developed for Compton camera imaging at present. In this study, we first quantitatively evaluated reconstructed Compton camera images of uniformly distributed diffuse sources, and then confirmed that our Compton camera obtained 3 %(1 σ) and 5 %(1 σ) uniformity for line and plane sources, respectively. Based on this quantitative study, we demonstrated on-line gamma imaging during proton irradiation. Through these studies, we show that the Compton camera is suitable for future use as an on-line monitor for particle therapy.

200 MeV Proton Radiography Studies with a Hand Phantom Using a Prototype Proton CT Scanner

PubMed Central

Plautz, Tia; Bashkirov, V.; Feng, V.; Hurley, F.; Johnson, R.P.; Leary, C.; Macafee, S.; Plumb, A.; Rykalin, V.; Sadrozinski, H.F.-W.; Schubert, K.; Schulte, R.; Schultze, B.; Steinberg, D.; Witt, M.; Zatserklyaniy, A.

2014-01-01

Proton radiography has applications in patient alignment and verification procedures for proton beam radiation therapy. In this paper, we report an experiment which used 200 MeV protons to generate proton energy-loss and scattering radiographs of a hand phantom. The experiment used the first-generation proton CT scanner prototype, which was installed on the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center (LLUMC). It was found that while both radiographs displayed anatomical details of the hand phantom, the energy-loss radiograph had a noticeably higher resolution. Nonetheless, scattering radiography may yield more contrast between soft and bone tissue than energy-loss radiography, however, this requires further study. This study contributes to the optimization of the performance of the next-generation of clinical proton CT scanners. Furthermore, it demonstrates the potential of proton imaging (proton radiography and CT), which is now within reach of becoming available as a new, potentially low-dose medical imaging modality. PMID:24710156

WE-D-BRB-00: Basics of Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

Incorporating deliverable monitor unit constraints into spot intensity optimization in intensity modulated proton therapy treatment planning

PubMed Central

Cao, Wenhua; Lim, Gino; Li, Xiaoqiang; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

2014-01-01

The purpose of this study is to investigate the feasibility and impact of incorporating deliverable monitor unit (MU) constraints into spot intensity optimization in intensity modulated proton therapy (IMPT) treatment planning. The current treatment planning system (TPS) for IMPT disregards deliverable MU constraints in the spot intensity optimization (SIO) routine. It performs a post-processing procedure on an optimized plan to enforce deliverable MU values that are required by the spot scanning proton delivery system. This procedure can create a significant dose distribution deviation between the optimized and post-processed deliverable plans, especially when small spot spacings are used. In this study, we introduce a two-stage linear programming (LP) approach to optimize spot intensities and constrain deliverable MU values simultaneously, i.e., a deliverable spot intensity optimization (DSIO) model. Thus, the post-processing procedure is eliminated and the associated optimized plan deterioration can be avoided. Four prostate cancer cases at our institution were selected for study and two parallel opposed beam angles were planned for all cases. A quadratic programming (QP) based model without MU constraints, i.e., a conventional spot intensity optimization (CSIO) model, was also implemented to emulate the commercial TPS. Plans optimized by both the DSIO and CSIO models were evaluated for five different settings of spot spacing from 3 mm to 7 mm. For all spot spacings, the DSIO-optimized plans yielded better uniformity for the target dose coverage and critical structure sparing than did the CSIO-optimized plans. With reduced spot spacings, more significant improvements in target dose uniformity and critical structure sparing were observed in the DSIO- than in the CSIO-optimized plans. Additionally, better sparing of the rectum and bladder was achieved when reduced spacings were used for the DSIO-optimized plans. The proposed DSIO approach ensures the deliverability of optimized IMPT plans that take into account MU constraints. This eliminates the post-processing procedure required by the TPS as well as the resultant deteriorating effect on ultimate dose distributions. This approach therefore allows IMPT plans to adopt all possible spot spacings optimally. Moreover, dosimetric benefits can be achieved using smaller spot spacings. PMID:23835656

Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fredriksson, Albin, E-mail: albin.fredriksson@raysearchlabs.com; Hårdemark, Björn; Forsgren, Anders

2015-07-15

Purpose: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. Methods: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goalsmore » to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. Results: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. Conclusions: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.« less

A randomized controlled trial of laparoscopic nissen fundoplication versus proton pump inhibitors for treatment of patients with chronic gastroesophageal reflux disease: One-year follow-up.

PubMed

Anvari, Mehran; Allen, Christopher; Marshall, John; Armstrong, David; Goeree, Ron; Ungar, Wendy; Goldsmith, Charles

2006-12-01

A randomized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor (n = 52) with laparoscopic Nissen fundoplication (n = 52). Patients were monitored for 1 year. The primary end point was frequency of gastroesophageal reflux dis-ease symptoms. Surgical patients had improved symptoms, pH control, and overall quality of life health index after surgery at 1 year compared with the medical group. The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients, but improved in the surgical patients. Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose, but 6 had satisfactory symptom remission. No surgical patients required additional treatment for symptom control. Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical candidates and should experience improved symptom control after surgery at 1 year.

Impact of respiratory motion on worst-case scenario optimized intensity modulated proton therapy for lung cancers.

PubMed

Liu, Wei; Liao, Zhongxing; Schild, Steven E; Liu, Zhong; Li, Heng; Li, Yupeng; Park, Peter C; Li, Xiaoqiang; Stoker, Joshua; Shen, Jiajian; Keole, Sameer; Anand, Aman; Fatyga, Mirek; Dong, Lei; Sahoo, Narayan; Vora, Sujay; Wong, William; Zhu, X Ronald; Bues, Martin; Mohan, Radhe

2015-01-01

We compared conventionally optimized intensity modulated proton therapy (IMPT) treatment plans against worst-case scenario optimized treatment plans for lung cancer. The comparison of the 2 IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient setup, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. For each of the 9 lung cancer cases, 2 treatment plans were created that accounted for treatment uncertainties in 2 different ways. The first used the conventional method: delivery of prescribed dose to the planning target volume that is geometrically expanded from the internal target volume (ITV). The second used a worst-case scenario optimization scheme that addressed setup and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of changes in patient anatomy attributable to respiratory motion were investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the 2 groups were compared with 2-sided paired Student t tests. Without respiratory motion considered, we affirmed that worst-case scenario optimization is superior to planning target volume-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, worst-case scenario optimization still achieved more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality (D95% ITV, 96.6% vs 96.1% [P = .26]; D5%- D95% ITV, 10.0% vs 12.3% [P = .082]; D1% spinal cord, 31.8% vs 36.5% [P = .035]). Worst-case scenario optimization led to superior solutions for lung IMPT. Despite the fact that worst-case scenario optimization did not explicitly account for respiratory motion, it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Schild, S; Bues, M

Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from themore » internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly account for respiratory motion it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization.« less

WE-D-BRB-03: Current State of Volumetric Image Guidance for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua, C.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-04: Clinical Applications of CBCT for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teo, B.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-01: Basic Physics of Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arjomandy, B.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

Influence of robust optimization in intensity-modulated proton therapy with different dose delivery techniques

PubMed Central

Liu, Wei; Li, Yupeng; Li, Xiaoqiang; Cao, Wenhua; Zhang, Xiaodong

2012-01-01

Purpose: The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique’s sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved. Methods: They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans’ sensitivity to uncertainties. Results: With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies. Conclusions: IMPT’s sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the optimization algorithm attempts to produce a single-field uniform dose distribution while minimizing the patching field as much as possible; and (2) perturbed dose distribution, which follows the change in anatomical geometry. Multiple-instance optimization has more knowledge of the influence matrices; this greater knowledge improves IMPT plans’ ability to retain robustness despite the presence of uncertainties. PMID:22755694

Partial response to proton pump inhibitor therapy for GERD: observational study of patient characteristics, burden of disease, and costs in the USA.

PubMed

Stålhammar, Nils-Olov; Spiegel, Brennan M; Granstedt Löfman, Helena; Karlsson, Maria; Wahlqvist, Peter; Næsdal, Jørgen; Nelson, M Todd; Despiégel, Nicolas

2012-01-01

Disease burden and associated costs are not well understood among patients with gastroesophageal reflux disease (GERD) who have persistent symptoms despite optimized proton pump inhibitor (PPI) therapy. The aim of this study was to investigate disease burden and costs of GERD in partial responders to PPI therapy. The Partial Response to PPI treatment: the Cost to Society and the Burden to the Patient in the US (REMAIN US) study was a 12-month, multicenter, noninterventional, observational study of 552 partial PPI responders in the USA. Participating sites were comprised of family practice (n = 30), internal medicine (n = 8), and specialist (gastroenterologist) centers (n = 15). GERD symptoms, health-related quality of life (HRQL), and impact on productivity were evaluated from patient-reported outcome instruments. Resource utilization data were also collected. Patients had a high symptom burden, impaired HRQL, and reduced productivity while at work and in daily activities, despite optimized PPI therapy. Mean annual GERD-related costs were US$9944 per patient, comprising total direct costs and mean productivity loss costs of US$4068 and US$5876 per patient, respectively. Patients with GERD and a partial response to PPI therapy have considerable direct and indirect costs, along with substantial impairments in HRQL and productivity.

Machine learning-based patient specific prompt-gamma dose monitoring in proton therapy

NASA Astrophysics Data System (ADS)

Gueth, P.; Dauvergne, D.; Freud, N.; Létang, J. M.; Ray, C.; Testa, E.; Sarrut, D.

2013-07-01

Online dose monitoring in proton therapy is currently being investigated with prompt-gamma (PG) devices. PG emission was shown to be correlated with dose deposition. This relationship is mostly unknown under real conditions. We propose a machine learning approach based on simulations to create optimized treatment-specific classifiers that detect discrepancies between planned and delivered dose. Simulations were performed with the Monte-Carlo platform Gate/Geant4 for a spot-scanning proton therapy treatment and a PG camera prototype currently under investigation. The method first builds a learning set of perturbed situations corresponding to a range of patient translation. This set is then used to train a combined classifier using distal falloff and registered correlation measures. Classifier performances were evaluated using receiver operating characteristic curves and maximum associated specificity and sensitivity. A leave-one-out study showed that it is possible to detect discrepancies of 5 mm with specificity and sensitivity of 85% whereas using only distal falloff decreases the sensitivity down to 77% on the same data set. The proposed method could help to evaluate performance and to optimize the design of PG monitoring devices. It is generic: other learning sets of deviations, other measures and other types of classifiers could be studied to potentially reach better performance. At the moment, the main limitation lies in the computation time needed to perform the simulations.

Clinical trial: factors associated with freedom from relapse of heartburn in patients with healed reflux oesophagitis--results from the maintenance phase of the EXPO study.

PubMed

Labenz, J; Armstrong, D; Zetterstrand, S; Eklund, S; Leodolter, A

2009-06-01

Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients. To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis. This post-hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH-NEG-0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once-daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse. Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P < 0.0001). Other factors significantly associated with freedom from heartburn relapse were Helicobacter pylori infection, greater age, non-obesity, absence of epigastric pain at baseline, pre-treatment nonsevere heartburn and GERD symptom duration < or =5 years. Several factors predict freedom from heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long-term symptom management in reflux oesophagitis patients.

SU-F-BRD-07: Fast Monte Carlo-Based Biological Optimization of Proton Therapy Treatment Plans for Thyroid Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Chan Tseung, H; Ma, J; Ma, D

2015-06-15

Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based biological planning for the treatment of thyroid tumors in spot-scanning proton therapy. Methods: Recently, we developed a fast and accurate GPU-based MC simulation of proton transport that was benchmarked against Geant4.9.6 and used as the dose calculation engine in a clinically-applicable GPU-accelerated IMPT optimizer. Besides dose, it can simultaneously score the dose-averaged LET (LETd), which makes fast biological dose (BD) estimates possible. To convert from LETd to BD, we used a linear relation based on cellular irradiation data. Given a thyroid patient with a 93cc tumor volume, we createdmore » a 2-field IMPT plan in Eclipse (Varian Medical Systems). This plan was re-calculated with our MC to obtain the BD distribution. A second 5-field plan was made with our in-house optimizer, using pre-generated MC dose and LETd maps. Constraints were placed to maintain the target dose to within 25% of the prescription, while maximizing the BD. The plan optimization and calculation of dose and LETd maps were performed on a GPU cluster. The conventional IMPT and biologically-optimized plans were compared. Results: The mean target physical and biological doses from our biologically-optimized plan were, respectively, 5% and 14% higher than those from the MC re-calculation of the IMPT plan. Dose sparing to critical structures in our plan was also improved. The biological optimization, including the initial dose and LETd map calculations, can be completed in a clinically viable time (∼30 minutes) on a cluster of 25 GPUs. Conclusion: Taking advantage of GPU acceleration, we created a MC-based, biologically optimized treatment plan for a thyroid patient. Compared to a standard IMPT plan, a 5% increase in the target’s physical dose resulted in ∼3 times as much increase in the BD. Biological planning was thus effective in escalating the target BD.« less

Incorporating uncertainty and motion in Intensity Modulated Radiation Therapy treatment planning

NASA Astrophysics Data System (ADS)

Martin, Benjamin Charles

In radiation therapy, one seeks to destroy a tumor while minimizing the damage to surrounding healthy tissue. Intensity Modulated Radiation Therapy (IMRT) uses overlapping beams of x-rays that add up to a high dose within the target and a lower dose in the surrounding healthy tissue. IMRT relies on optimization techniques to create high quality treatments. Unfortunately, the possible conformality is limited by the need to ensure coverage even if there is organ movement or deformation. Currently, margins are added around the tumor to ensure coverage based on an assumed motion range. This approach does not ensure high quality treatments. In the standard IMRT optimization problem, an objective function measures the deviation of the dose from the clinical goals. The optimization then finds the beamlet intensities that minimize the objective function. When modeling uncertainty, the dose delivered from a given set of beamlet intensities is a random variable. Thus the objective function is also a random variable. In our stochastic formulation we minimize the expected value of this objective function. We developed a problem formulation that is both flexible and fast enough for use on real clinical cases. While working on accelerating the stochastic optimization, we developed a technique of voxel sampling. Voxel sampling is a randomized algorithms approach to a steepest descent problem based on estimating the gradient by only calculating the dose to a fraction of the voxels within the patient. When combined with an automatic sampling rate adaptation technique, voxel sampling produced an order of magnitude speed up in IMRT optimization. We also develop extensions of our results to Intensity Modulated Proton Therapy (IMPT). Due to the physics of proton beams the stochastic formulation yields visibly different and better plans than normal optimization. The results of our research have been incorporated into a software package OPT4D, which is an IMRT and IMPT optimization tool that we developed.

Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunn, G. Brandon; Blanchard, Pierre; Department of Radiation Oncology, Institut Gustave Roussy, Villejuif

Purpose: A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer. Methods and Materials: Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration. Results: Fifty patients with OPC treated from March 3, 2011, to July 2014 formed the cohort. Eighty-four percent were male, 50% had never smoked, 98% had stagemore » III/IV disease, 64% received concurrent therapy, and 35% received induction chemotherapy. Forty-four of 45 tumors (98%) tested for p16 were positive. All patients received IMPT (multifield optimization to n=46; single-field optimization to n=4). No Common Terminology Criteria for Adverse Events grade 4 or 5 toxicities were observed. The most common grade 3 toxicities were acute mucositis in 58% of patients and late dysphagia in 12%. Eleven patients had a gastrostomy (feeding) tube placed during therapy, but none had a feeding tube at last follow-up. At a median follow-up time of 29 months, 5 patients had disease recurrence: local in 1, local and regional in 1, regional in 2, and distant in 1. The 2-year actuarial overall and progression-free survival rates were 94.5% and 88.6%. Conclusions: The oncologic, toxicity, and functional outcomes after IMPT for OPC are encouraging and provide the basis for ongoing and future clinical studies.« less

Effect of elemental compositions on Monte Carlo dose calculations in proton therapy of eye tumors

NASA Astrophysics Data System (ADS)

Rasouli, Fatemeh S.; Farhad Masoudi, S.; Keshazare, Shiva; Jette, David

2015-12-01

Recent studies in eye plaque brachytherapy have found considerable differences between the dosimetric results by using a water phantom, and a complete human eye model. Since the eye continues to be simulated as water-equivalent tissue in the proton therapy literature, a similar study for investigating such a difference in treating eye tumors by protons is indispensable. The present study inquires into this effect in proton therapy utilizing Monte Carlo simulations. A three-dimensional eye model with elemental compositions is simulated and used to examine the dose deposition to the phantom. The beam is planned to pass through a designed beam line to moderate the protons to the desired energies for ocular treatments. The results are compared with similar irradiation to a water phantom, as well as to a material with uniform density throughout the whole volume. Spread-out Bragg peaks (SOBPs) are created by adding pristine peaks to cover a typical tumor volume. Moreover, the corresponding beam parameters recommended by the ICRU are calculated, and the isodose curves are computed. The results show that the maximum dose deposited in ocular media is approximately 5-7% more than in the water phantom, and about 1-1.5% less than in the homogenized material of density 1.05 g cm-3. Furthermore, there is about a 0.2 mm shift in the Bragg peak due to the tissue composition difference between the models. It is found that using the weighted dose profiles optimized in a water phantom for the realistic eye model leads to a small disturbance of the SOBP plateau dose. In spite of the plaque brachytherapy results for treatment of eye tumors, it is found that the differences between the simplified models presented in this work, especially the phantom containing the homogenized material, are not clinically significant in proton therapy. Taking into account the intrinsic uncertainty of the patient dose calculation for protons, and practical problems corresponding to applying patient-specific eye modeling, we found that the results of using a generic phantom containing homogenized material for proton therapy of eye tumors can be satisfactory for designing the beam.

WE-F-16A-03: 3D Printer Application in Proton Therapy: A Novel Method to Deliver Passive-Scattering Proton Beams with a Fixed Range and Modulation for SRS and SRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, X; Witztum, A; Liang, X

2014-06-15

Purpose: To present a novel technique to deliver passive-scattering proton beam with fixed range and modulation using a 3D printed patient-specific bolus for proton stereotactic radiosurgery and radiotherapy. Methods: A CIRS head phantom was used to simulate a patient with a small brain lesion. A custom bolus was created in the Eclipse Treatment Planning System (TPS) to compensate for the different water equivalent depths from the patient surface to the target from multiple beam directions. To simulate arc therapy, a plan was created on the initial CT using three passive-scattering proton beams with a fixed range and modulations irradiating frommore » different angles. The DICOM-RT structure file of the bolus was exported from the TPS and converted to STL format for 3D printing. The phantom was rescanned with the printed custom bolus and head cup to verify the dose distribution comparing to the initial plan. EBT3 films were placed in the sagital plane of the target to verify the delivered dose distribution. The relative stopping power of the printing material(ABSplus-P430) was measured using the Zebra multi-plate ion chamber. Results: The relative stopping power of the 3D printing material, ABSplus-P430 was 1.05 which is almost water equivalent. The dose difference between verification CT and Initial CT is almost negligible. Film measurement also confirmed the accuracy for this new proton delivery technique. Conclusion: Our method using 3D printed range modifiers simplify the treatment delivery of multiple passive-scattering beams in treatment of small lesion in brain. This technique makes delivery of multiple beam more efficient and can be extended to allow arc therapy with proton beams. The ability to create and construct complex patient specific bolus structures provides a new dimension in creating optimized quality treatment plans not only for proton therapy but also for electron and photon therapy.« less

When to Wait for More Evidence? Real Options Analysis in Proton Therapy

PubMed Central

Abrams, Keith R.; de Ruysscher, Dirk; Pijls-Johannesma, Madelon; Peters, Hans J.M.; Beutner, Eric; Lambin, Philippe; Joore, Manuela A.

2011-01-01

Purpose. Trends suggest that cancer spending growth will accelerate. One method for controlling costs is to examine whether the benefits of new technologies are worth the extra costs. However, especially new and emerging technologies are often more costly, while limited clinical evidence of superiority is available. In that situation it is often unclear whether to adopt the new technology now, with the risk of investing in a suboptimal therapy, or to wait for more evidence, with the risk of withholding patients their optimal treatment. This trade-off is especially difficult when it is costly to reverse the decision to adopt a technology, as is the case for proton therapy. Real options analysis, a technique originating from financial economics, assists in making this trade-off. Methods. We examined whether to adopt proton therapy, as compared to stereotactic body radiotherapy, in the treatment of inoperable stage I non-small cell lung cancer. Three options are available: adopt without further research; adopt and undertake a trial; or delay adoption and undertake a trial. The decision depends on the expected net gain of each option, calculated by subtracting its total costs from its expected benefits. Results. In The Netherlands, adopt and trial was found to be the preferred option, with an optimal sample size of 200 patients. Increase of treatment costs abroad and costs of reversal altered the preferred option. Conclusion. We have shown that real options analysis provides a transparent method of weighing the costs and benefits of adopting and/or further researching new and expensive technologies. PMID:22147003

SU-D-304-06: Measurement of LET in Patient-Specific Proton Therapy Treatment Fields Using Optically Stimulated Luminescence Detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Granville, DA; Sahoo, N; Sawakuchi, GO

Purpose: To investigate the use of optically stimulated luminescence (OSL) detectors (OSLDs) for measurements of dose-averaged linear energy transfer (LET) in patient-specific proton therapy treatment fields. Methods: We used Al{sub 2}O{sub 3}:C OSLDs made from the same material as commercially available nanoDot OSLDs from Landauer, Inc. We calibrated two parameters of the OSL signal as functions of LET in therapeutic proton beams: the ratio of the ultraviolet and blue emission intensities (UV/blue ratio) and the OSL curve shape. These calibration curves were created by irradiating OSLDs in passively scattered beams of known LET (0.96 to 3.91 keV/µm). The LET valuesmore » were determined using a validated Monte Carlo model of the beamline. We then irradiated new OSLDs with the prescription dose (16 to 74 cGy absorbed dose to water) at the center of the spread-out Bragg peak (SOBP) of four patient-specific treatment fields. From readouts of these OSLDs, we determined both the UV/blue ratio and OSL curve shape parameters. Combining these parameters with the calibration curves, we were able to measure LET using the OSLDs. The measurements were compared to the theoretical LET values obtained from Monte Carlo simulations of the patient-specific treatments fields. Results: Using the UV/blue ratio parameter, we were able to measure LET within 3.8%, 6.2%, 5.6% and 8.6% of the Monte Carlo value for each of the patient fields. Similarly, using the OSL curve shape parameter, LET measurements agreed within 0.5%, 11.0%, 2.5% and 7.6% for each of the four fields. Conclusion: We have demonstrated a method to verify LET in patient-specific proton therapy treatment fields using OSLDs. The possibility of enhancing biological effectiveness of proton therapy treatment plans by including LET in the optimization has been previously shown. The LET verification method we have demonstrated will be useful in the quality assurance of such LET optimized treatment plans. DA Granville received financial support from the Natural Sciences and Engineering Research Council of Canada.« less

Pitfalls of tungsten multileaf collimator in proton beam therapy.

PubMed

Moskvin, Vadim; Cheng, Chee-Wai; Das, Indra J

2011-12-01

Particle beam therapy is associated with significant startup and operational cost. Multileaf collimator (MLC) provides an attractive option to improve the efficiency and reduce the treatment cost. A direct transfer of the MLC technology from external beam radiation therapy is intuitively straightforward to proton therapy. However, activation, neutron production, and the associated secondary cancer risk in proton beam should be an important consideration which is evaluated. Monte Carlo simulation with FLUKA particle transport code was applied in this study for a number of treatment models. The authors have performed a detailed study of the neutron generation, ambient dose equivalent [H∗(10)], and activation of a typical tungsten MLC and compared with those obtained from a brass aperture used in a typical proton therapy system. Brass aperture and tungsten MLC were modeled by absorber blocks in this study, representing worst-case scenario of a fully closed collimator. With a tungsten MLC, the secondary neutron dose to the patient is at least 1.5 times higher than that from a brass aperture. The H∗(10) from a tungsten MLC at 10 cm downstream is about 22.3 mSv/Gy delivered to water phantom by noncollimated 200 MeV beam of 20 cm diameter compared to 14 mSv/Gy for the brass aperture. For a 30-fraction treatment course, the activity per unit volume in brass aperture reaches 5.3 × 10⁴ Bq cm(-3) at the end of the last treatment. The activity in brass decreases by a factor of 380 after 24 h, additional 6.2 times after 40 days of cooling, and is reduced to background level after 1 yr. Initial activity in tungsten after 30 days of treating 30 patients per day is about 3.4 times higher than in brass that decreases only by a factor of 2 after 40 days and accumulates to 1.2 × 10⁶ Bq cm(-3) after a full year of operation. The daily utilization of the MLC leads to buildup of activity with time. The overall activity continues to increase due to (179)Ta with a half-life of 1.82 yr and thus require prolonged storage for activity cooling. The H∗(10) near the patient side of the tungsten block is about 100 μSv/h and is 27 times higher at the upstream side of the block. This would lead to an accumulated dose for therapists in a year that may exceed occupational maximum permissible dose (50 mSv/yr). The value of H∗(10) at the upstream surface of the tungsten block is about 220 times higher than that of the brass. MLC is an efficient way for beam shaping and overall cost reduction device in proton therapy. However, based on this study, tungsten seems to be not an optimal material for MLC in proton beam therapy. Usage of tungsten MLC in clinic may create unnecessary risks associated with the secondary neutrons and induced radioactivity for patients and staff depending on the patient load. A careful selection of material for manufacturing of an optimal MLC for proton therapy is thus desired.

Fast multipurpose Monte Carlo simulation for proton therapy using multi- and many-core CPU architectures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souris, Kevin, E-mail: kevin.souris@uclouvain.be; Lee, John Aldo; Sterpin, Edmond

2016-04-15

Purpose: Accuracy in proton therapy treatment planning can be improved using Monte Carlo (MC) simulations. However the long computation time of such methods hinders their use in clinical routine. This work aims to develop a fast multipurpose Monte Carlo simulation tool for proton therapy using massively parallel central processing unit (CPU) architectures. Methods: A new Monte Carlo, called MCsquare (many-core Monte Carlo), has been designed and optimized for the last generation of Intel Xeon processors and Intel Xeon Phi coprocessors. These massively parallel architectures offer the flexibility and the computational power suitable to MC methods. The class-II condensed history algorithmmore » of MCsquare provides a fast and yet accurate method of simulating heavy charged particles such as protons, deuterons, and alphas inside voxelized geometries. Hard ionizations, with energy losses above a user-specified threshold, are simulated individually while soft events are regrouped in a multiple scattering theory. Elastic and inelastic nuclear interactions are sampled from ICRU 63 differential cross sections, thereby allowing for the computation of prompt gamma emission profiles. MCsquare has been benchmarked with the GATE/GEANT4 Monte Carlo application for homogeneous and heterogeneous geometries. Results: Comparisons with GATE/GEANT4 for various geometries show deviations within 2%–1 mm. In spite of the limited memory bandwidth of the coprocessor simulation time is below 25 s for 10{sup 7} primary 200 MeV protons in average soft tissues using all Xeon Phi and CPU resources embedded in a single desktop unit. Conclusions: MCsquare exploits the flexibility of CPU architectures to provide a multipurpose MC simulation tool. Optimized code enables the use of accurate MC calculation within a reasonable computation time, adequate for clinical practice. MCsquare also simulates prompt gamma emission and can thus be used also for in vivo range verification.« less

Including robustness in multi-criteria optimization for intensity-modulated proton therapy

NASA Astrophysics Data System (ADS)

Chen, Wei; Unkelbach, Jan; Trofimov, Alexei; Madden, Thomas; Kooy, Hanne; Bortfeld, Thomas; Craft, David

2012-02-01

We present a method to include robustness in a multi-criteria optimization (MCO) framework for intensity-modulated proton therapy (IMPT). The approach allows one to simultaneously explore the trade-off between different objectives as well as the trade-off between robustness and nominal plan quality. In MCO, a database of plans each emphasizing different treatment planning objectives, is pre-computed to approximate the Pareto surface. An IMPT treatment plan that strikes the best balance between the different objectives can be selected by navigating on the Pareto surface. In our approach, robustness is integrated into MCO by adding robustified objectives and constraints to the MCO problem. Uncertainties (or errors) of the robust problem are modeled by pre-calculated dose-influence matrices for a nominal scenario and a number of pre-defined error scenarios (shifted patient positions, proton beam undershoot and overshoot). Objectives and constraints can be defined for the nominal scenario, thus characterizing nominal plan quality. A robustified objective represents the worst objective function value that can be realized for any of the error scenarios and thus provides a measure of plan robustness. The optimization method is based on a linear projection solver and is capable of handling large problem sizes resulting from a fine dose grid resolution, many scenarios, and a large number of proton pencil beams. A base-of-skull case is used to demonstrate the robust optimization method. It is demonstrated that the robust optimization method reduces the sensitivity of the treatment plan to setup and range errors to a degree that is not achieved by a safety margin approach. A chordoma case is analyzed in more detail to demonstrate the involved trade-offs between target underdose and brainstem sparing as well as robustness and nominal plan quality. The latter illustrates the advantage of MCO in the context of robust planning. For all cases examined, the robust optimization for each Pareto optimal plan takes less than 5 min on a standard computer, making a computationally friendly interface possible to the planner. In conclusion, the uncertainty pertinent to the IMPT procedure can be reduced during treatment planning by optimizing plans that emphasize different treatment objectives, including robustness, and then interactively seeking for a most-preferred one from the solution Pareto surface.

Range optimization for mono- and bi-energetic proton modulated arc therapy with pencil beam scanning

NASA Astrophysics Data System (ADS)

Sanchez-Parcerisa, Daniel; Kirk, Maura; Fager, Marcus; Burgdorf, Brendan; Stowe, Malorie; Solberg, Tim; Carabe, Alejandro

2016-11-01

The development of rotational proton therapy plans based on a pencil-beam-scanning (PBS) system has been limited, among several other factors, by the energy-switching time between layers, a system-dependent parameter that ranges between a fraction of a second and several seconds. We are investigating mono- and bi-energetic rotational proton modulated arc therapy (PMAT) solutions that would not be affected by long energy switching times. In this context, a systematic selection of the optimal proton energy for each arc is vital. We present a treatment planning comparison of four different range selection methods, analyzing the dosimetric outcomes of the resulting treatment plans created with the ranges obtained. Given the patient geometry and arc definition (gantry and couch trajectories, snout elevation) our in-house treatment planning system (TPS) FoCa was used to find the maximum, medial and minimum water-equivalent thicknesses (WETs) of the target viewed from all possible field orientations. Optimal ranges were subsequently determined using four methods: (1) by dividing the max/min WET interval into equal steps, (2) by taking the average target midpoints from each field, (3) by taking the average WET of all voxels from all field orientations, and (4) by minimizing the fraction of the target which cannot be reached from any of the available angles. After the range (for mono-energetic plans) or ranges (for bi-energetic plans) were selected, the commercial clinical TPS in use in our institution (Varian Eclipse™) was used to produce the PMAT plans using multifield optimization. Linear energy transfer (LET) distributions of all plans were also calculated using FoCa and compared among the different methods. Mono- and bi-energetic PMAT plans, composed of a single 180° arc, were created for two patient geometries: a C-shaped target located in the mediastinal area of a thoracic tissue-equivalent phantom and a small brain tumor located directly above the brainstem. All plans were optimized using the same procedure to (1) achieve target coverage, (2) reduce dose to OAR and (3) limit dose hot spots in the target. Final outcomes were compared in terms of the resulting dose and LET distributions. Data shows little significant differences among the four studied methods, with superior results obtained with mono-energetic plans. A streamlined systematic method has been implemented in an in-house TPS to find the optimal range to maximize target coverage with rotational mono- or bi-energetic PBS rotational plans by minimizing the fraction of the target that cannot be reached by any direction.

Secondary Neutron Doses to Pediatric Patients During Intracranial Proton Therapy: Monte Carlo Simulation of the Neutron Energy Spectrum and its Organ Doses.

PubMed

Matsumoto, Shinnosuke; Koba, Yusuke; Kohno, Ryosuke; Lee, Choonsik; Bolch, Wesley E; Kai, Michiaki

2016-04-01

Proton therapy has the physical advantage of a Bragg peak that can provide a better dose distribution than conventional x-ray therapy. However, radiation exposure of normal tissues cannot be ignored because it is likely to increase the risk of secondary cancer. Evaluating secondary neutrons generated by the interaction of the proton beam with the treatment beam-line structure is necessary; thus, performing the optimization of radiation protection in proton therapy is required. In this research, the organ dose and energy spectrum were calculated from secondary neutrons using Monte Carlo simulations. The Monte Carlo code known as the Particle and Heavy Ion Transport code System (PHITS) was used to simulate the transport proton and its interaction with the treatment beam-line structure that modeled the double scattering body of the treatment nozzle at the National Cancer Center Hospital East. The doses of the organs in a hybrid computational phantom simulating a 5-y-old boy were calculated. In general, secondary neutron doses were found to decrease with increasing distance to the treatment field. Secondary neutron energy spectra were characterized by incident neutrons with three energy peaks: 1×10, 1, and 100 MeV. A block collimator and a patient collimator contributed significantly to organ doses. In particular, the secondary neutrons from the patient collimator were 30 times higher than those from the first scatter. These results suggested that proactive protection will be required in the design of the treatment beam-line structures and that organ doses from secondary neutrons may be able to be reduced.

SU-E-T-07: 4DCT Robust Optimization for Esophageal Cancer Using Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, L; Department of Industrial Engineering, University of Houston, Houston, TX; Yu, J

2015-06-15

Purpose: To develop a 4DCT robust optimization method to reduce the dosimetric impact from respiratory motion in intensity modulated proton therapy (IMPT) for esophageal cancer. Methods: Four esophageal cancer patients were selected for this study. The different phases of CT from a set of 4DCT were incorporated into the worst-case dose distribution robust optimization algorithm. 4DCT robust treatment plans were designed and compared with the conventional non-robust plans. Result doses were calculated on the average and maximum inhale/exhale phases of 4DCT. Dose volume histogram (DVH) band graphic and ΔD95%, ΔD98%, ΔD5%, ΔD2% of CTV between different phases were used tomore » evaluate the robustness of the plans. Results: Compare to the IMPT plans optimized using conventional methods, the 4DCT robust IMPT plans can achieve the same quality in nominal cases, while yield a better robustness to breathing motion. The mean ΔD95%, ΔD98%, ΔD5% and ΔD2% of CTV are 6%, 3.2%, 0.9% and 1% for the robustly optimized plans vs. 16.2%, 11.8%, 1.6% and 3.3% from the conventional non-robust plans. Conclusion: A 4DCT robust optimization method was proposed for esophageal cancer using IMPT. We demonstrate that the 4DCT robust optimization can mitigate the dose deviation caused by the diaphragm motion.« less

Design of Linear Accelerator (LINAC) tanks for proton therapy via Particle Swarm Optimization (PSO) and Genetic Algorithm (GA) approaches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castellano, T.; De Palma, L.; Laneve, D.

2015-07-01

A homemade computer code for designing a Side- Coupled Linear Accelerator (SCL) is written. It integrates a simplified model of SCL tanks with the Particle Swarm Optimization (PSO) algorithm. The computer code main aim is to obtain useful guidelines for the design of Linear Accelerator (LINAC) resonant cavities. The design procedure, assisted via the aforesaid approach seems very promising, allowing future improvements towards the optimization of actual accelerating geometries. (authors)

MO-A-201-01: A Cliff’s Notes Version of Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kruse, J.

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatchesmore » between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ from standard x-ray approaches, due to equipment design or the desire to maximize efficiency within a high-cost proton therapy treatment room. Differences between x-ray and proton therapy delivery will be described. Learning Objectives: Understand how CT HU are calibrated to provide proton stopping power, and the sources of uncertainty in this process. Understand why a PTV is not suitable for proton therapy, and how robust treatment planning and evaluation are used to mitigate uncertainties. Understand the source and implications of variable RBE in proton therapy Learn about proton specific challenges and approaches in beam delivery and image guidance Jon Kruse has a research grant from Varian Medical Systems related to proton therapy treatment plannning.; J. Kruse, Jon Kruse has a research grant with Varian Medical Systems related to proton therapy planning.« less

MO-A-201-00: A Cliff’s Notes Version of Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatchesmore » between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ from standard x-ray approaches, due to equipment design or the desire to maximize efficiency within a high-cost proton therapy treatment room. Differences between x-ray and proton therapy delivery will be described. Learning Objectives: Understand how CT HU are calibrated to provide proton stopping power, and the sources of uncertainty in this process. Understand why a PTV is not suitable for proton therapy, and how robust treatment planning and evaluation are used to mitigate uncertainties. Understand the source and implications of variable RBE in proton therapy Learn about proton specific challenges and approaches in beam delivery and image guidance Jon Kruse has a research grant from Varian Medical Systems related to proton therapy treatment plannning.; J. Kruse, Jon Kruse has a research grant with Varian Medical Systems related to proton therapy planning.« less

A Project of Boron Neutron Capture Therapy System based on a Proton Linac Neutron Source

NASA Astrophysics Data System (ADS)

Kiyanagi, Yoshikai; Asano, Kenji; Arakawa, Akihiro; Fukuchi, Shin; Hiraga, Fujio; Kimura, Kenju; Kobayashi, Hitoshi; Kubota, Michio; Kumada, Hiroaki; Matsumoto, Hiroshi; Matsumoto, Akira; Sakae, Takeji; Saitoh, Kimiaki; Shibata, Tokushi; Yoshioka, Masakazu

At present, the clinical trials of Boron Neutron Capture Therapy (BNCT) are being performed at research reactor facilities. However, an accelerator based BNCT has a merit that it can be built in a hospital. So, we just launched a development project for the BNCT based on an accelerator in order to establish and to spread the BNCT as an effective therapy in the near future. In the project, a compact proton linac installed in a hospital will be applied as a neutron source, and energy of the proton beam is planned to be less than about 10 MeV to reduce the radioactivity. The BNCT requires epithermal neutron beam with an intensity of around 1x109 (n/cm2/sec) to deliver the therapeutic dose to a deeper region in a body and to complete the irradiation within an hour. From this condition, the current of the proton beam required is estimated to be a few mA on average. Enormous heat deposition in the target is a big issue. We are aiming at total optimization of the accelerator based BNCT from the linac to the irradiation position. Here, the outline of the project is introduced and the moderator design is presented.

SU-E-T-663: Radiation Properties of a Water-Equivalent Material Formulated Using the Stoichiometric Analysis Method in Heavy Charged Particle Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yohannes, I; Vasiliniuc, S; Hild, S

2015-06-15

Purpose: A material has been designed to be employed as water-equivalent in particle therapy using a previously established stoichiometric analysis method (SAM). After manufacturing, experimental verification of the material’s water-equivalent path length (WEPL) and analysis of its total inelastic nuclear interaction cross sections for proton beams were performed. Methods: Using the SAM, we optimized the material composed of three base materials, i.e., polyurethane, calcium carbonate and microspheres. From the elemental composition of the compound, electron density, linear attenuation coefficients, particle stopping powers and inelastic nuclear cross sections for protons using data from ICRU 63 were calculated. The calculations were thenmore » compared to Hounsfield units (HUs) measured with 350 mAs at 80, 100, 120 and 140 kV and the WEPLs measured with three different ions: proton (106.8 MeV/u), helium (107.93 MeV/u) and carbon (200.3 MeV/u). Results: The material’s measured HUs (0.7±3.0 to 2.6±6.2 HU) as well as its calculated relative electron density (1.0001) are in close agreement with water as reference. The WEPLs measured on a 20.00 mm thick target were 20.16±0.12, 20.29±0.12 and 20.38±0.12 mmH2O for proton, helium and carbon ions, respectively. Within measurement uncertainties, these values verified the calculated WEPLs of 20.28 mmH2O (proton), 20.28 mmH2O (helium) and 20.26 mmH2O (carbon). Moreover, the calculated proton inelastic cross sections of the material differed only by 0.89% (100 MeV/u) and 0.01% (200 MeV/u) when compared to water. Conclusion: The SAM is capable of optimizing material with defined properties, e.g., HU, electron density, WEPL and inelastic nuclear interaction cross section for particle therapy. Such material will have a wide range of applications amongst others absolute dosimetry. This work was supported by grant ZIM KF2137107AK4 from the German Federal Ministry for Economic Affairs and Energy.« less

Proton therapy for locally advanced breast cancer: A systematic review of the literature.

PubMed

Kammerer, Emmanuel; Guevelou, Jennifer Le; Chaikh, Abdulhamid; Danhier, Serge; Geffrelot, Julien; Levy, Christelle; Saloux, Eric; Habrand, Jean-Louis; Thariat, Juliette

2018-02-01

Radiation therapy plays a major role in the management of adjuvant breast cancer with nodal involvement, with an iatrogenic increase of cardio-vascular risk. Photon therapy, even with intensity modulation, has the downsides of high mean heart dose and heterogeneous target coverage, particularly in the case of internal mammary irradiation. This systematic review of the literature aims to evaluate proton therapy in locally advanced breast cancer. PubMed was searched for original full-text articles with the following search terms: «Proton Therapy» and «Breast Cancer». On-going trials were collected using the words "Breast Cancer" and "Protons". 13 articles met the criteria: 6 with passive proton therapy (Double Scattering), 5 with Pencil Beam Scanning (PBS) and 2 with a combination of both. Proton therapy offered a better target coverage than photons, even compared with intensity modulation radiation therapy (including static or rotational IMRT or tomotherapy). With proton therapy, volumes receiving 95% of the dose were around 98%, with low volumes receiving 105% of the dose. Proton therapy often decreased mean heart dose by a factor of 2 or 3, i.e. 1 Gy with proton therapy versus 3 Gy with conventional 3D, and 6 Gy for IMRT. Lungs were better spared with proton therapy than with photon therapy. Cutaneous toxicity observed with double scattering is improved with PBS. Proton therapy reduces mean heart dose in breast cancer irradiation, probably reducing late cardio-vascular toxicity. Large clinical studies will likely confirm a clinical benefit of proton therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Uncertainty reduction in intensity modulated proton therapy by inverse Monte Carlo treatment planning

NASA Astrophysics Data System (ADS)

Morávek, Zdenek; Rickhey, Mark; Hartmann, Matthias; Bogner, Ludwig

2009-08-01

Treatment plans for intensity-modulated proton therapy may be sensitive to some sources of uncertainty. One source is correlated with approximations of the algorithms applied in the treatment planning system and another one depends on how robust the optimization is with regard to intra-fractional tissue movements. The irradiated dose distribution may substantially deteriorate from the planning when systematic errors occur in the dose algorithm. This can influence proton ranges and lead to improper modeling of the Braggpeak degradation in heterogeneous structures or particle scatter or the nuclear interaction part. Additionally, systematic errors influence the optimization process, which leads to the convergence error. Uncertainties with regard to organ movements are related to the robustness of a chosen beam setup to tissue movements on irradiation. We present the inverse Monte Carlo treatment planning system IKO for protons (IKO-P), which tries to minimize the errors described above to a large extent. Additionally, robust planning is introduced by beam angle optimization according to an objective function penalizing paths representing strongly longitudinal and transversal tissue heterogeneities. The same score function is applied to optimize spot planning by the selection of a robust choice of spots. As spots can be positioned on different energy grids or on geometric grids with different space filling factors, a variety of grids were used to investigate the influence on the spot-weight distribution as a result of optimization. A tighter distribution of spot weights was assumed to result in a more robust plan with respect to movements. IKO-P is described in detail and demonstrated on a test case and a lung cancer case as well. Different options of spot planning and grid types are evaluated, yielding a superior plan quality with dose delivery to the spots from all beam directions over optimized beam directions. This option shows a tighter spot-weight distribution and should therefore be less sensitive to movements compared to optimized directions. But accepting a slight loss in plan quality, the latter choice could potentially improve robustness even further by accepting only spots from the most proper direction. The choice of a geometric grid instead of an energy grid for spot positioning has only a minor influence on the plan quality, at least for the investigated lung case.

SU-F-T-195: Systematic Constraining of Contralateral Parotid Gland Led to Improved Dosimetric Outcomes for Multi-Field Optimization with Scanning Beam Proton Therapy: Promising Results From a Pilot Study in Patients with Base of Tongue Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, R; Liu, A; Poenisch, F

Purpose: Treatment planning for Intensity Modulated Proton Therapy (IMPT) for head and neck cancer is time-consuming due to the large number of organs-at-risk (OAR) to be considered. As there are many competing objectives and also wide range of acceptable OAR constraints, the final approved plan may not be most optimal for the given structures. We evaluated the dose reduction to the contralateral parotid by implementing standardized constraints during optimization for scanning beam proton therapy planning. Methods: Twenty-four (24) consecutive patients previously treated for base of tongue carcinoma were retrospectively selected. The doses were 70Gy, 63Gy and 57Gy (SIB in 33more » fractions) for high-, intermediate-, and standard-risk clinical target volumes (CTV), respectively; the treatment included bilateral neck. Scanning beams using MFO with standardized bilateral anterior oblique and PA fields were applied. New plans where then developed and optimized by employing additional contralateral parotid constraints at multiple defined dose levels. Using a step-wise iterative process, the volume-based constraints at each level were then further reduced until known target coverages were compromised. The newly developed plans were then compared to the original clinically approved plans using paired student t-testing. Results: All 24 newly optimized treatment plans maintained initial plan quality as compared to the approved plans, and the 98% prescription dose coverage to the CTV’s were not compromised. Representative DVH comparison is shown in FIGURE 1. The contralateral parotid doses were reduced at all levels of interest when systematic constraints were applied to V10, V20, V30 and V40Gy (All P<0.0001; TABLE 1). Overall, the mean contralateral parotid doses were reduced by 2.26 Gy on average, a ∼13% relative improvement. Conclusion: Applying systematic and volume-based contralateral parotid constraints for IMPT planning significantly reduced the dose at all dosimetric levels for patients with base of tongue cancer.« less

The clinical case for proton beam therapy

PubMed Central

2012-01-01

Abstract Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence Proton beam therapy is a technically advanced and promising form of radiation therapy. PMID:23083010

Proton Beam Therapy

NASA Astrophysics Data System (ADS)

Paganetti, Harald

2017-01-01

Cancer therapy is a multi-modality approach including surgery, systemic or targeted chemotherapy, radiation (external beam or radionuclide), and immunotherapy. Radiation is typically administered using external beam photon therapy. Proton therapy has been around for more than 60 years but was restricted to research laboratories until the 1990s. Since then clinical proton therapy has been growing rapidly with currently more than 50 facilities worldwide. The interest in proton therapy stems from the physical properties of protons allowing for advanced dose sculpting around the target and sparing of healthy tissue. This review first evaluates the basics of proton therapy physics and technology and then outlines some of the current physical, biological, and clinical challenges. Solving these will ultimately determine whether proton therapy will continue on its path to becoming mainstream.

The physics of proton therapy.

PubMed

Newhauser, Wayne D; Zhang, Rui

2015-04-21

The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy.

The physics of proton therapy

PubMed Central

Newhauser, Wayne D; Zhang, Rui

2015-01-01

The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy. PMID:25803097

Proton therapy in clinical practice

PubMed Central

Liu, Hui; Chang, Joe Y.

2011-01-01

Radiation dose escalation and acceleration improves local control but also increases toxicity. Proton radiation is an emerging therapy for localized cancers that is being sought with increasing frequency by patients. Compared with photon therapy, proton therapy spares more critical structures due to its unique physics. The physical properties of a proton beam make it ideal for clinical applications. By modulating the Bragg peak of protons in energy and time, a conformal radiation dose with or without intensity modulation can be delivered to the target while sparing the surrounding normal tissues. Thus, proton therapy is ideal when organ preservation is a priority. However, protons are more sensitive to organ motion and anatomy changes compared with photons. In this article, we review practical issues of proton therapy, describe its image-guided treatment planning and delivery, discuss clinical outcome for cancer patients, and suggest challenges and the future development of proton therapy. PMID:21527064

Proton Therapy for Head and Neck Cancer.

PubMed

Kim, Joseph K; Leeman, Jonathan E; Riaz, Nadeem; McBride, Sean; Tsai, Chiaojung Jillian; Lee, Nancy Y

2018-05-09

The application of proton beam radiation therapy in the treatment of head and neck cancer has grown tremendously in the past few years. Globally, widespread interest in proton beam therapy has led to multiple research efforts regarding its therapeutic value and cost-effectiveness. The current standard of care using modern photon radiation technology has demonstrated excellent treatment outcomes, yet there are some situations where disease control remains suboptimal with the potential for detrimental acute and chronic toxicities. Due to the advantageous physical properties of the proton beam, proton beam therapy may be superior to photon therapy in some patient subsets for both disease control and patient quality of life. As enthusiasm and excitement for proton beam therapy continue to increase, clinical research and widespread adoption will elucidate the true value of proton beam therapy and give a greater understanding of the full risks and benefits of proton therapy in head and neck cancer.

Development of a Multileaf Collimator for Proton Radiotherapy

DTIC Science & Technology

2007-06-01

for proton radiotherapy, and the first year of the project to develop image guided treatment protocols for proton therapy . This research...multileaf collimator (MLC) for proton therapy and investigates the issues that must be resolved to use an MLC in proton therapy . The second technology...the contract included three development agreements directly related to the work supported by this grant to develop technology for proton therapy .

SU-G-TeP2-13: Patient-Specific Reduction of Range Uncertainties in Proton Therapy by Proton Radiography with a Multi-Layer Ionization Chamber

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deffet, S; Macq, B; Farace, P

2016-06-15

Purpose: The conversion from Hounsfield units (HU) to stopping powers is a major source of range uncertainty in proton therapy (PT). Our contribution shows how proton radiographs (PR) acquired with a multi-layer ionization chamber in a PT center can be used for accurate patient positioning and subsequently for patient-specific optimization of the conversion from HU to stopping powers. Methods: A multi-layer ionization chamber was used to measure the integral depth-dose (IDD) of 220 MeV pencil beam spots passing through several anthropomorphic phantoms. The whole area of interest was imaged by repositioning the couch and by acquiring a 45×45 mm{sup 2}more » frame for each position. A rigid registration algorithm was implemented to correct the positioning error between the proton radiographs and the planning CT. After registration, the stopping power map obtained from the planning CT with the calibration curve of the treatment planning system was used together with the water equivalent thickness gained from two proton radiographs to generate a phantom-specific stopping power map. Results: Our results show that it is possible to make a registration with submillimeter accuracy from proton radiography obtained by sending beamlets separated by more than 1 mm. This was made possible by the complex shape of the IDD due to the presence of lateral heterogeneities along the path of the beam. Submillimeter positioning was still possible with a 5 mm spot spacing. Phantom specific stopping power maps obtained by minimizing the range error were cross-verified by the acquisition of an additional proton radiography where the phantom was positioned in a random but known manner. Conclusion: Our results indicate that a CT-PR registration algorithm together with range-error based optimization can be used to produce a patient-specific stopping power map. Sylvain Deffet reports financial funding of its PhD thesis by Ion Beam Applications (IBA) during the confines of the study and outside the submitted work. Francois Vander Stappen reports being employed by Ion Beam Applications (IBA) during the confines of the study and outside the submitted work.« less

Monte Carlo calculations in support of the commissioning of the Northeast Proton Therapy Center.

PubMed

Flanz, J; Paganetti, H

2003-12-01

Monte Carlo studies were conducted related to the design of the Northeast Proton Therapy Center (NPTC). These studies were also helpful for commissioning the beam delivery performance of the facility. The calculations included preventing proton leakage from the beam delivery nozzle, anomalies in the dose distributions and studies, which could influence future beam delivery techniques. Using simulations it was possible to reduce the proton leakage by over an order of magnitude, while minimizing the weight of the assembly. Interestingly, the thickness of the brass shielding has no influence on the secondary neutron radiation since the number of generated neutrons is almost independent of the amount of brass if the primary beam is completely stopped. Monte Carlo simulations are able to study the effect of small beam misalignments with respect to apertures in the nozzle. Such tolerances are very difficult to define experimentally. Studying the effects of nuclear interactions we showed that, if the dose distributions would be optimized theoretically using the primary proton dose alone, there would be about a 5 % dose increase at the proximal end of a SOBP. In radiobiology studies we found that the RBE at beam entrance increases due to the build-up of the secondary particle fluence.

Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chaudhary, Pankaj; Marshall, Thomas I.; Perozziello, Francesca M.

2014-09-01

Purpose: The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate themore » RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials: Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results: We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton biological effectiveness. Data were also used to validate a parameterized RBE model. Conclusions: The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.« less

Optimization of dual-energy CT acquisitions for proton therapy using projection-based decomposition.

PubMed

Vilches-Freixas, Gloria; Létang, Jean Michel; Ducros, Nicolas; Rit, Simon

2017-09-01

Dual-energy computed tomography (DECT) has been presented as a valid alternative to single-energy CT to reduce the uncertainty of the conversion of patient CT numbers to proton stopping power ratio (SPR) of tissues relative to water. The aim of this work was to optimize DECT acquisition protocols from simulations of X-ray images for the treatment planning of proton therapy using a projection-based dual-energy decomposition algorithm. We have investigated the effect of various voltages and tin filtration combinations on the SPR map accuracy and precision, and the influence of the dose allocation between the low-energy (LE) and the high-energy (HE) acquisitions. For all spectra combinations, virtual CT projections of the Gammex phantom were simulated with a realistic energy-integrating detector response model. Two situations were simulated: an ideal case without noise (infinite dose) and a realistic situation with Poisson noise corresponding to a 20 mGy total central dose. To determine the optimal dose balance, the proportion of LE-dose with respect to the total dose was varied from 10% to 90% while keeping the central dose constant, for four dual-energy spectra. SPR images were derived using a two-step projection-based decomposition approach. The ranges of 70 MeV, 90 MeV, and 100 MeV proton beams onto the adult female (AF) reference computational phantom of the ICRP were analytically determined from the reconstructed SPR maps. The energy separation between the incident spectra had a strong impact on the SPR precision. Maximizing the incident energy gap reduced image noise. However, the energy gap was not a good metric to evaluate the accuracy of the SPR. In terms of SPR accuracy, a large variability of the optimal spectra was observed when studying each phantom material separately. The SPR accuracy was almost flat in the 30-70% LE-dose range, while the precision showed a minimum slightly shifted in favor of lower LE-dose. Photon noise in the SPR images (20 mGy dose) had lower impact on the proton range accuracy as comparable results were obtained for the noiseless situation (infinite dose). Root-mean-square range errors averaged over all irradiation angles associated to dual-energy imaging were comprised between 0.50 mm and 0.72 mm for the noiseless situation and between 0.51 mm and 0.77 mm for the realistic scenario. The impact of the dual-energy spectra and the dose allocation between energy levels on the SPR accuracy and precision determined through a projection-based dual-energy algorithm were evaluated to guide the choice of spectra for dual-energy CT for proton therapy. The dose balance between energy levels was not found to be sensitive for the SPR estimation. The optimal pair of dual-energy spectra was material dependent but on a heterogeneous anthropomorphic phantom, there was no significant difference in range accuracy and the choice of spectra could be driven by the precision, i.e., the energy gap. © 2017 American Association of Physicists in Medicine.

Management of Gastroesophageal Reflux Disease.

PubMed

Gyawali, C Prakash; Fass, Ronnie

2018-01-01

Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Proton therapy may allow for comprehensive elective nodal coverage for patients receiving neoadjuvant radiotherapy for localized pancreatic head cancers.

PubMed

Lee, Richard Y; Nichols, Romaine C; Huh, Soon N; Ho, Meng W; Li, Zuofeng; Zaiden, Robert; Awad, Ziad T; Ahmed, Bestoun; Hoppe, Bradfors S

2013-12-01

Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly increasing critical normal-tissue exposure in the neoadjuvant setting.

Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl; Kooy, Hanne M.; Heijmen, Ben J.M.

2015-06-01

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases.more » Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.« less

National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, Kristin A., E-mail: kristin.higgins@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; O'Connell, Kelli

Purpose: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. Methods and Materials: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. Results: A total of 243,822more » patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). Conclusions: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.« less

Computational simulation of natUO2, 232ThO2 and U3O8-Al pills to estimate (p,fission) 99Mo yield in the modeled targets irradiated by CYCLONE30 accelerator.

PubMed

Jozvaziri, Atieh; Gholamzadeh, Zohreh; Yousefi, Kamran; Mirvakili, Seyed Mohammad; Alizadeh, Masoomeh; Aboudzadeh, Mohammadreza

2017-03-01

99 Mo is important for both therapy and imaging purposes. Accelerator and reactor-based procedures are applied to produce it. Newly proton-fission method has been taken in attention by some research centers. In the present work, computationally investigation of the 99 Mo yield in different fissionable targets irradiated by proton was aimed. The results showed UO 2 pill target could be efficiently used to produce 11.12Ci/g-U saturation yield of 99 Mo using 25MeV proton irradiation of the optimized-dimension target with 70µA current. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-F-T-186: A Treatment Planning Study of Normal Tissue Sparing with Robustness Optimized IMPT, 4Pi IMRT, and VMAT for Head and Neck Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, J; Li, X; Ding, X

Purpose: We performed a retrospective dosimetric comparison study between the robustness optimized Intensity Modulated Proton Therapy (RO-IMPT), volumetric-modulated arc therapy (VMAT), and the non-coplanar 4? intensity modulated radiation therapy (IMRT). These methods represent the most advanced radiation treatment methods clinically available. We compare their dosimetric performance for head and neck cancer treatments with special focus on the OAR sparing near the tumor volumes. Methods: A total of 11 head and neck cases, which include 10 recurrent cases and one bilateral case, were selected for the study. Different dose levels were prescribed to tumor target depending on disease and location. Threemore » treatment plans were created on commercial TPS systems for a novel noncoplanar 4π method (20 beams), VMAT, and RO-IMPT technique (maximum 4 fields). The maximum patient positioning error was set to 3 mm and the maximum proton range uncertainty was set to 3% for the robustness optimization. Line dose profiles were investigated for OARs close to tumor volumes. Results: All three techniques achieved 98% coverage of the CTV target and most photon plans had less than 110% of the hot spots. The RO-IMPT plans show superior tumor dose homogeneity than 4? and VMAT plans. Although RO-IMPT has greater R50 dose spillage to the surrounding normal tissue than 4π and VMAT, the RO-IMPT plans demonstrate better or comparable OAR (parotid, mandible, carotid, oral cavity, pharynx, and etc.) sparing for structures closely abutting tumor targets. Conclusion: The RO-IMPT’s ability of OAR sparing is benchmarked against the C-arm linac based non-coplanar 4π technique and the standard VMAT method. RO-IMPT consistently shows better or comparable OAR sparing even for tissue structures closely abutting treatment target volume. RO-IMPT further reduces treatment uncertainty associated with proton therapy and delivers robust treatment plans to both unilateral and bilateral head and neck cancer patients with desirable treatment time.« less

Proton Therapy Verification with PET Imaging

PubMed Central

Zhu, Xuping; Fakhri, Georges El

2013-01-01

Proton therapy is very sensitive to uncertainties introduced during treatment planning and dose delivery. PET imaging of proton induced positron emitter distributions is the only practical approach for in vivo, in situ verification of proton therapy. This article reviews the current status of proton therapy verification with PET imaging. The different data detecting systems (in-beam, in-room and off-line PET), calculation methods for the prediction of proton induced PET activity distributions, and approaches for data evaluation are discussed. PMID:24312147

Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barragán, A. M., E-mail: ana.barragan@uclouvain.be; Differding, S.; Lee, J. A.

Purpose: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. Methods: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTV{sub PET}) was calculated from {sup 18}FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number ofmore » fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTV{sub PET} inevitably leads to overdosing, which was compared for both optimization schemes. Results: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTV{sub PET} (worst case) were above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. Conclusions: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.« less

Influence of beam efficiency through the patient-specific collimator on secondary neutron dose equivalent in double scattering and uniform scanning modes of proton therapy.

PubMed

Hecksel, D; Anferov, V; Fitzek, M; Shahnazi, K

2010-06-01

Conventional proton therapy facilities use double scattering nozzles, which are optimized for delivery of a few fixed field sizes. Similarly, uniform scanning nozzles are commissioned for a limited number of field sizes. However, cases invariably occur where the treatment field is significantly different from these fixed field sizes. The purpose of this work was to determine the impact of the radiation field conformity to the patient-specific collimator on the secondary neutron dose equivalent. Using a WENDI-II neutron detector, the authors experimentally investigated how the neutron dose equivalent at a particular point of interest varied with different collimator sizes, while the beam spreading was kept constant. The measurements were performed for different modes of dose delivery in proton therapy, all of which are available at the Midwest Proton Radiotherapy Institute (MPRI): Double scattering, uniform scanning delivering rectangular fields, and uniform scanning delivering circular fields. The authors also studied how the neutron dose equivalent changes when one changes the amplitudes of the scanned field for a fixed collimator size. The secondary neutron dose equivalent was found to decrease linearly with the collimator area for all methods of dose delivery. The relative values of the neutron dose equivalent for a collimator with a 5 cm diameter opening using 88 MeV protons were 1.0 for the double scattering field, 0.76 for rectangular uniform field, and 0.6 for the circular uniform field. Furthermore, when a single circle wobbling was optimized for delivery of a uniform field 5 cm in diameter, the secondary neutron dose equivalent was reduced by a factor of 6 compared to the double scattering nozzle. Additionally, when the collimator size was kept constant, the neutron dose equivalent at the given point of interest increased linearly with the area of the scanned proton beam. The results of these experiments suggest that the patient-specific collimator is a significant contributor to the secondary neutron dose equivalent to a distant organ at risk. Improving conformity of the radiation field to the patient-specific collimator can significantly reduce secondary neutron dose equivalent to the patient. Therefore, it is important to increase the number of available generic field sizes in double scattering systems as well as in uniform scanning nozzles.

[Why proton therapy? And how?

PubMed

Thariat, Juliette; Habrand, Jean Louis; Lesueur, Paul; Chaikh, Abdulhamid; Kammerer, Emmanuel; Lecomte, Delphine; Batalla, Alain; Balosso, Jacques; Tessonnier, Thomas

2018-03-01

Proton therapy is a radiotherapy, based on the use of protons, charged subatomic particles that stop at a given depth depending on their initial energy (pristine Bragg peak), avoiding any output beam, unlike the photons used in most of the other modalities of radiotherapy. Proton therapy has been used for 60 years, but has only become ubiquitous in the last decade because of recent major advances in particle accelerator technology. This article reviews the history of clinical implementation of protons, the nature of the technological advances that now allows its expansion at a lower cost. It also addresses the technical and physical specificities of proton therapy and the clinical situations for which proton therapy may be relevant but requires evidence. Different proton therapy techniques are possible. These are explained in terms of their clinical potential by explaining the current terminology (such as cyclotrons, synchrotrons or synchrocyclotrons, using superconducting magnets, fixed line or arm rotary with passive diffusion delivery or active by scanning) in basic words. The requirements associated with proton therapy are increased due to the precision of the depth dose deposit. The learning curve of proton therapy requires that clinical indications be prioritized according to their associated uncertainties (such as range uncertainties and movement in lung tumors). Many clinical indications potentially fall under proton therapy ultimately. Clinical strategies are explained in a paralleled manuscript. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Special cases for proton beam radiotherapy: re-irradiation, lymphoma, and breast cancer.

PubMed

Plastaras, John P; Berman, Abigail T; Freedman, Gary M

2014-12-01

The dose distributions that can be achieved with protons are usually superior to those of conventional photon external-beam radiation. There are special cases where proton therapy may offer a substantial potential benefit compared to photon treatments where toxicity concerns dominate. Re-irradiation may theoretically be made safer with proton therapy due to lower cumulative lifetime doses to sensitive tissues, such as the spinal cord. Proton therapy has been used in a limited number of patients with rectal, pancreatic, esophageal, and lung cancers. Chordomas and soft tissue sarcomas require particularly high radiation doses, posing additional challenges for re-irradiation. Lymphoma is another special case where proton therapy may be advantageous. Late toxicities from even relatively low radiation doses, including cardiac complications and second cancers, are of concern in lymphoma patients with high cure rates and long life expectancies. Proton therapy has begun to be used for consolidation after chemotherapy in patients with Hodgkin and non-Hodgkin lymphoma. Breast cancer is another emerging area of proton therapy development and use. Proton therapy may offer advantages compared to other techniques in the setting of breast boosts, accelerated partial breast irradiation, and post-mastectomy radiotherapy. In these settings, proton therapy may decrease toxicity associated with breast radiotherapy. As techniques are refined in proton therapy, we may be able to improve the therapeutic ratio by maintaining the benefits of radiotherapy while better minimizing the risks. Copyright © 2014 Elsevier Inc. All rights reserved.

Integrated beam orientation and scanning-spot optimization in intensity-modulated proton therapy for brain and unilateral head and neck tumors.

PubMed

Gu, Wenbo; O'Connor, Daniel; Nguyen, Dan; Yu, Victoria Y; Ruan, Dan; Dong, Lei; Sheng, Ke

2018-04-01

Intensity-Modulated Proton Therapy (IMPT) is the state-of-the-art method of delivering proton radiotherapy. Previous research has been mainly focused on optimization of scanning spots with manually selected beam angles. Due to the computational complexity, the potential benefit of simultaneously optimizing beam orientations and spot pattern could not be realized. In this study, we developed a novel integrated beam orientation optimization (BOO) and scanning-spot optimization algorithm for intensity-modulated proton therapy (IMPT). A brain chordoma and three unilateral head-and-neck patients with a maximal target size of 112.49 cm 3 were included in this study. A total number of 1162 noncoplanar candidate beams evenly distributed across 4π steradians were included in the optimization. For each candidate beam, the pencil-beam doses of all scanning spots covering the PTV and a margin were calculated. The beam angle selection and spot intensity optimization problem was formulated to include three terms: a dose fidelity term to penalize the deviation of PTV and OAR doses from ideal dose distribution; an L1-norm sparsity term to reduce the number of active spots and improve delivery efficiency; a group sparsity term to control the number of active beams between 2 and 4. For the group sparsity term, convex L2,1-norm and nonconvex L2,1/2-norm were tested. For the dose fidelity term, both quadratic function and linearized equivalent uniform dose (LEUD) cost function were implemented. The optimization problem was solved using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA). The IMPT BOO method was tested on three head-and-neck patients and one skull base chordoma patient. The results were compared with IMPT plans created using column generation selected beams or manually selected beams. The L2,1-norm plan selected spatially aggregated beams, indicating potential degeneracy using this norm. L2,1/2-norm was able to select spatially separated beams and achieve smaller deviation from the ideal dose. In the L2,1/2-norm plans, the [mean dose, maximum dose] of OAR were reduced by an average of [2.38%, 4.24%] and[2.32%, 3.76%] of the prescription dose for the quadratic and LEUD cost function, respectively, compared with the IMPT plan using manual beam selection while maintaining the same PTV coverage. The L2,1/2 group sparsity plans were dosimetrically superior to the column generation plans as well. Besides beam orientation selection, spot sparsification was observed. Generally, with the quadratic cost function, 30%~60% spots in the selected beams remained active. With the LEUD cost function, the percentages of active spots were in the range of 35%~85%.The BOO-IMPT run time was approximately 20 min. This work shows the first IMPT approach integrating noncoplanar BOO and scanning-spot optimization in a single mathematical framework. This method is computationally efficient, dosimetrically superior and produces delivery-friendly IMPT plans. © 2018 American Association of Physicists in Medicine.

Universal field matching in craniospinal irradiation by a background-dose gradient-optimized method.

PubMed

Traneus, Erik; Bizzocchi, Nicola; Fellin, Francesco; Rombi, Barbara; Farace, Paolo

2018-01-01

The gradient-optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient-optimized technique, based on the use of a background dose, is described. Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An 'in silico' ideal background dose was created first to cover the upper-spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower-spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper-spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on. In both proton and photon plans, the optimized cranial and the lower-spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper-spinal beam. The final dose distributions showed a homogeneous coverage of the targets. Our simple technique allowed to obtain high-quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Novel scintillation detector design and performance for proton radiography and computed tomography.

PubMed

Bashkirov, V A; Schulte, R W; Hurley, R F; Johnson, R P; Sadrozinski, H F-W; Zatserklyaniy, A; Plautz, T; Giacometti, V

2016-02-01

Proton computed tomography (pCT) will enable accurate prediction of proton and ion range in a patient while providing the benefit of lower radiation exposure than in x-ray CT. The accuracy of the range prediction is essential for treatment planning in proton or ion therapy and depends upon the detector used to evaluate the water-equivalent path length (WEPL) of a proton passing through the object. A novel approach is presented for an inexpensive WEPL detector for pCT and proton radiography. A novel multistage detector with an aperture of 10 × 37.5 cm was designed to optimize the accuracy of the WEPL measurements while simplifying detector construction and the performance requirements of its components. The design of the five-stage detector was optimized through simulations based on the geant4 detector simulation toolkit, and the fabricated prototype was calibrated in water-equivalent millimeters with 200 MeV protons in the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center. A special polystyrene step phantom was designed and built to speed up and simplify the calibration procedure. The calibrated five-stage detector was tested in the 200 MeV proton beam as part of the pCT head scanner, using a water phantom and polystyrene slabs to verify the WEPL reconstruction accuracy. The beam-test results demonstrated excellent performance of the new detector, in good agreement with the simulation results. The WEPL measurement accuracy is about 3.0 mm per proton in the 0-260 mm WEPL range required for a pCT head scan with a 200 MeV proton beam. The new multistage design approach to WEPL measurements for proton CT and radiography has been prototyped and tested. The test results show that the design is competitive with much more expensive calorimeter and range-counter designs.

Novel scintillation detector design and performance for proton radiography and computed tomography

PubMed Central

Schulte, R. W.; Hurley, R. F.; Johnson, R. P.; Sadrozinski, H. F.-W.; Zatserklyaniy, A.; Plautz, T.; Giacometti, V.

2016-01-01

Purpose: Proton computed tomography (pCT) will enable accurate prediction of proton and ion range in a patient while providing the benefit of lower radiation exposure than in x-ray CT. The accuracy of the range prediction is essential for treatment planning in proton or ion therapy and depends upon the detector used to evaluate the water-equivalent path length (WEPL) of a proton passing through the object. A novel approach is presented for an inexpensive WEPL detector for pCT and proton radiography. Methods: A novel multistage detector with an aperture of 10 × 37.5 cm was designed to optimize the accuracy of the WEPL measurements while simplifying detector construction and the performance requirements of its components. The design of the five-stage detector was optimized through simulations based on the geant4 detector simulation toolkit, and the fabricated prototype was calibrated in water-equivalent millimeters with 200 MeV protons in the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center. A special polystyrene step phantom was designed and built to speed up and simplify the calibration procedure. The calibrated five-stage detector was tested in the 200 MeV proton beam as part of the pCT head scanner, using a water phantom and polystyrene slabs to verify the WEPL reconstruction accuracy. Results: The beam-test results demonstrated excellent performance of the new detector, in good agreement with the simulation results. The WEPL measurement accuracy is about 3.0 mm per proton in the 0–260 mm WEPL range required for a pCT head scan with a 200 MeV proton beam. Conclusions: The new multistage design approach to WEPL measurements for proton CT and radiography has been prototyped and tested. The test results show that the design is competitive with much more expensive calorimeter and range-counter designs. PMID:26843230

TU-EF-304-10: Efficient Multiscale Simulation of the Proton Relative Biological Effectiveness (RBE) for DNA Double Strand Break (DSB) Induction and Bio-Effective Dose in the FLUKA Monte Carlo Radiation Transport Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moskvin, V; Tsiamas, P; Axente, M

2015-06-15

Purpose: One of the more critical initiating events for reproductive cell death is the creation of a DNA double strand break (DSB). In this study, we present a computationally efficient way to determine spatial variations in the relative biological effectiveness (RBE) of proton therapy beams within the FLUKA Monte Carlo (MC) code. Methods: We used the independently tested Monte Carlo Damage Simulation (MCDS) developed by Stewart and colleagues (Radiat. Res. 176, 587–602 2011) to estimate the RBE for DSB induction of monoenergetic protons, tritium, deuterium, hellium-3, hellium-4 ions and delta-electrons. The dose-weighted (RBE) coefficients were incorporated into FLUKA to determinemore » the equivalent {sup 6}°60Co γ-ray dose for representative proton beams incident on cells in an aerobic and anoxic environment. Results: We found that the proton beam RBE for DSB induction at the tip of the Bragg peak, including primary and secondary particles, is close to 1.2. Furthermore, the RBE increases laterally to the beam axis at the area of Bragg peak. At the distal edge, the RBE is in the range from 1.3–1.4 for cells irradiated under aerobic conditions and may be as large as 1.5–1.8 for cells irradiated under anoxic conditions. Across the plateau region, the recorded RBE for DSB induction is 1.02 for aerobic cells and 1.05 for cells irradiated under anoxic conditions. The contribution to total effective dose from secondary heavy ions decreases with depth and is higher at shallow depths (e.g., at the surface of the skin). Conclusion: Multiscale simulation of the RBE for DSB induction provides useful insights into spatial variations in proton RBE within pristine Bragg peaks. This methodology is potentially useful for the biological optimization of proton therapy for the treatment of cancer. The study highlights the need to incorporate spatial variations in proton RBE into proton therapy treatment plans.« less

Cost of New Technologies in Prostate Cancer Treatment: Systematic Review of Costs and Cost Effectiveness of Robotic-assisted Laparoscopic Prostatectomy, Intensity-modulated Radiotherapy, and Proton Beam Therapy.

PubMed

Schroeck, Florian Rudolf; Jacobs, Bruce L; Bhayani, Sam B; Nguyen, Paul L; Penson, David; Hu, Jim

2017-11-01

Some of the high costs of robot-assisted radical prostatectomy (RARP), intensity-modulated radiotherapy (IMRT), and proton beam therapy may be offset by better outcomes or less resource use during the treatment episode. To systematically review the literature to identify the key economic trade-offs implicit in a particular treatment choice for prostate cancer. We systematically reviewed the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement and protocol. We searched Medline, Embase, and Web of Science for articles published between January 2001 and July 2016, which compared the treatment costs of RARP, IMRT, or proton beam therapy to the standard treatment. We identified 37, nine, and three studies, respectively. RARP is costlier than radical retropubic prostatectomy for hospitals and payers. However, RARP has the potential for a moderate cost advantage for payers and society over a longer time horizon when optimal cancer and quality-of-life outcomes are achieved. IMRT is more expensive from a payer's perspective compared with three-dimensional conformal radiotherapy, but also more cost effective when defined by an incremental cost effectiveness ratio <$50 000 per quality-adjusted life year. Proton beam therapy is costlier than IMRT and its cost effectiveness remains unclear given the limited comparative data on outcomes. Using the Grades of Recommendation, Assessment, Development and Evaluation approach, the quality of evidence was low for RARP and IMRT, and very low for proton beam therapy. Treatment with new versus traditional technologies is costlier. However, given the low quality of evidence and the inconsistencies across studies, the precise difference in costs remains unclear. Attempts to estimate whether this increased cost is worth the expense are hampered by the uncertainty surrounding improvements in outcomes, such as cancer control and side effects of treatment. If the new technologies can consistently achieve better outcomes, then they may be cost effective. We review the cost and cost effectiveness of robot-assisted radical prostatectomy, intensity-modulated radiotherapy, and proton beam therapy in prostate cancer treatment. These technologies are costlier than their traditional counterparts. It remains unclear whether their use is associated with improved cure and reduced morbidity, and whether the increased cost is worth the expense. Published by Elsevier B.V.

SU-D-BRC-05: Effects of Motion and Variable RBE in a Lung Patient Treated with Passively Scattered Protons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirkovic, D; Titt, U; Mohan, R

2016-06-15

Purpose: To evaluate effects of motion and variable relative biological effectiveness (RBE) in a lung cancer patient treated with passively scattered proton therapy using dose volume histograms associated with patient dose computed using three different methods. Methods: A proton treatment plan of a lung cancer patient optimized using clinical treatment planning system (TPS) was used to construct a detailed Monte Carlo (MC) model of the beam delivery system and the patient specific aperture and compensator. A phase space file containing all particles transported through the beam line was collected at the distal surface of the range compensator and subsequently transportedmore » through two different patient models. The first model was based on the average CT used by the TPS and the second model included all 10 phases of the corresponding 4DCT. The physical dose and proton linear energy transfer (LET) were computed in each voxel of two models and used to compute constant and variable RBE MC dose on average CT and 4D CT. The MC computed doses were compared to the TPS dose using dose volume histograms for relevant structures. Results: The results show significant differences in doses to the target and critical structures suggesting the need for more accurate proton dose computation methods. In particular, the 4D dose shows reduced coverage of the target and higher dose to the spinal cord, while variable RBE dose shows higher lung dose. Conclusion: The methodology developed in this pilot study is currently used for the analysis of a cohort of ∼90 lung patients from a clinical trial comparing proton and photon therapy for lung cancer. The results from this study will help us in determining the clinical significance of more accurate dose computation models in proton therapy.« less

Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma

PubMed Central

Conklin, Heather M.; Scoggins, Matthew A.; Ashford, Jason M.; Merchant, Thomas E.; Mandrell, Belinda N.; Ogg, Robert J.; Curtis, Elizabeth; Wise, Merrill S.; Indelicato, Daniel J.; Crabtree, Valerie M.

2016-01-01

Objective: Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy. Methods: Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy. Results: EDS was identified in 76% of the patients and was significantly related to increased HI extent (p = .04). There was no relationship between CPT performance during fMRI and HI or EDS. Visual examination of group composite fMRI images revealed greater spatial extent of activation in frontal cortical regions in patients with EDS, consistent with a compensatory activation hypothesis. Conclusion: Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity. PMID:27189690

MONDO: A tracker for the characterization of secondary fast and ultrafast neutrons emitted in particle therapy

NASA Astrophysics Data System (ADS)

Mirabelli, R.; Battistoni, G.; Giacometti, V.; Patera, V.; Pinci, D.; Sarti, A.; Sciubba, A.; Traini, G.; Marafini, M.

2018-01-01

In Particle Therapy (PT) accelerated charged particles and light ions are used for treating tumors. One of the main limitation to the precision of PT is the emission of secondary particles due to the beam interaction with the patient: secondary emitted neutrons can release a significant dose far from the tumor. Therefore, a precise characterization of their flux, production energy and angle distribution is eagerly needed in order to improve the Treatment Planning Systems (TPS) codes. The principal aim of the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project is the development of a tracking device optimized for the detection of fast and ultra-fast secondary neutrons emitted in PT. The detector consists of a matrix of scintillating square fibres coupled with a CMOS-based readout. Here, we present the characterization of the detector tracker prototype and CMOS-based digital SPAD (Single Photon Avalanche Diode) array sensor tested with protons at the Beam Test Facility (Frascati, Italy) and at the Proton Therapy Centre (Trento, Italy), respectively.

Socioeconomic factors affect the selection of proton radiation therapy for children.

PubMed

Shen, Colette J; Hu, Chen; Ladra, Matthew M; Narang, Amol K; Pollack, Craig E; Terezakis, Stephanie A

2017-10-15

Proton radiotherapy remains a limited resource despite its clear potential for reducing radiation doses to normal tissues and late effects in children in comparison with photon therapy. This study examined the impact of race and socioeconomic factors on the use of proton therapy in children with solid malignancies. This study evaluated 12,101 children (age ≤ 21 years) in the National Cancer Data Base who had been diagnosed with a solid malignancy between 2004 and 2013 and had received photon- or proton-based radiotherapy. Logistic regression analysis was used to evaluate patient, tumor, and socioeconomic variables affecting treatment with proton radiotherapy versus photon radiotherapy. Eight percent of the patients in the entire cohort received proton radiotherapy, and this proportion increased between 2004 (1.7%) and 2013 (17.5%). Proton therapy was more frequently used in younger patients (age ≤ 10 years; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.2) and in patients with bone/joint primaries and ependymoma, medulloblastoma, and rhabdomyosarcoma histologies (P < .05). Patients with metastatic disease were less likely to receive proton therapy (OR, 0.4; 95% CI, 0.3-0.6). Patients with private/managed care were more likely than patients with Medicaid or no insurance to receive proton therapy (P < .0001). A higher median household income and educational attainment were also associated with increased proton use (P < .001). Patients treated with proton therapy versus photon therapy were more likely to travel more than 200 miles (13% vs 5%; P < .0001). Socioeconomic factors affect the use of proton radiotherapy in children. Whether this disparity is related to differences in the referral patterns, the knowledge of treatment modalities, or the ability to travel for therapy needs to be further clarified. Improving access to proton therapy in underserved pediatric populations is essential. Cancer 2017;123:4048-56. © 2017 American Cancer Society. © 2017 American Cancer Society.

TH-CD-209-05: Impact of Spot Size and Spacing On the Quality of Robustly-Optimized Intensity-Modulated Proton Therapy Plans for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Ding, X; Hu, Y

Purpose: To investigate how spot size and spacing affect plan quality, especially, plan robustness and the impact of interplay effect, of robustly-optimized intensity-modulated proton therapy (IMPT) plans for lung cancer. Methods: Two robustly-optimized IMPT plans were created for 10 lung cancer patients: (1) one for a proton beam with in-air energy dependent large spot size at isocenter (σ: 5–15 mm) and spacing (1.53σ); (2) the other for a proton beam with small spot size (σ: 2–6 mm) and spacing (5 mm). Both plans were generated on the average CTs with internal-gross-tumor-volume density overridden to irradiate internal target volume (ITV). Themore » root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under RVH curves were used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Dose-volume-histogram indices including ITV coverage, homogeneity, and organs-at-risk (OAR) sparing were compared using Student-t test. Results: Compared to large spots, small spots resulted in significantly better OAR sparing with comparable ITV coverage and homogeneity in the nominal plan. Plan robustness was comparable for ITV and most OARs. With interplay effect considered, significantly better OAR sparing with comparable ITV coverage and homogeneity is observed using smaller spots. Conclusion: Robust optimization with smaller spots significantly improves OAR sparing with comparable plan robustness and similar impact of interplay effect compare to larger spots. Small spot size requires the use of larger number of spots, which gives optimizer more freedom to render a plan more robust. The ratio between spot size and spacing was found to be more relevant to determine plan robustness and the impact of interplay effect than spot size alone. This research was supported by the National Cancer Institute Career Developmental Award K25CA168984, by the Fraternal Order of Eagles Cancer Research Fund Career Development Award, by The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, by Mayo Arizona State University Seed Grant, and by The Kemper Marley Foundation.« less

Supine craniospinal irradiation in pediatric patients by proton pencil beam scanning.

PubMed

Farace, Paolo; Bizzocchi, Nicola; Righetto, Roberto; Fellin, Francesco; Fracchiolla, Francesco; Lorentini, Stefano; Widesott, Lamberto; Algranati, Carlo; Rombi, Barbara; Vennarini, Sabina; Amichetti, Maurizio; Schwarz, Marco

2017-04-01

Proton therapy is the emerging treatment modality for craniospinal irradiation (CSI) in pediatric patients. Herein, special methods adopted for CSI at proton Therapy Center of Trento by pencil beam scanning (PBS) are comprehensively described. Twelve pediatric patients were treated by proton PBS using two/three isocenters. Special methods refer to: (i) patient positioning in supine position on immobilization devices crossed by the beams; (ii) planning field-junctions via the ancillary-beam technique; (iii) achieving lens-sparing by three-beams whole-brain-irradiation; (iv) applying a movable-snout and beam-splitting technique to reduce the lateral penumbra. Patient-specific quality assurance (QA) program was performed using two-dimensional ion chamber array and γ-analysis. Daily kilovoltage alignment was performed. PBS allowed to obtain optimal target coverage (mean D98%>98%) with reduced dose to organs-at-risk. Lens sparing was obtained (mean D1∼730cGyE). Reducing lateral penumbra decreased the dose to the kidneys (mean Dmean<600cGyE). After kilovoltage alignment, potential dose deviations in the upper and lower junctions were small (average 0.8% and 1.2% respectively). Due to imperfect modeling of range shifter, QA showed better agreements between measurements and calculations at depths >4cm (mean γ>95%) than at depths<4cm. The reported methods allowed to effectively perform proton PBS CSI. Copyright © 2017 Elsevier B.V. All rights reserved.

Present Status and Future Developments in Proton Therapy

NASA Astrophysics Data System (ADS)

Smith, Alfred R.

2009-07-01

Within the past few years, interest in proton therapy has significantly increased. This interest has been generated by a number of factors including: 1) the reporting of positive clinical results using proton beams; 2) approval of reimbursement for delivery of proton therapy; 3) the success of hospital-based proton therapy centers; and 4) the availability of modern, integrated proton therapy technology for hospital-based facilities. In the United States, this increased interest has occurred particularly at the level of smaller academic hospitals, community medical centers, and large private practices; however, interest from large academic centers continues to be strong. Particular interest exists regarding smaller and less-expensive proton therapy systems, especially the so-called "single-room" systems. In this paper, the advantages and disadvantages of 1-room proton therapy systems will be discussed. The emphasis on smaller and cheaper proton therapy facilities has also generated interest in new proton-accelerating technologies such as superconducting cyclotrons and synchrocyclotrons, laser acceleration, and dielectric-wall accelerators. Superconducting magnets are also being developed to decrease the size and weight of isocentric gantries. Another important technical development is spot-beam scanning, which offers the ability to deliver intensity-modulated proton treatments (IMPT). IMPT has the potential to provide dose distributions that are superior to those for photon intensity modulation techniques (IMXT) and to improve clinical outcomes for patients undergoing cancer therapy. At the present time, only two facilities—one in Europe and one in the United States—have the ability to deliver IMPT treatments, however, within the next year or two several additional facilities are expected to achieve this capability.

A critical appraisal of the clinical utility of proton therapy in oncology

PubMed Central

Wang, Dongxu

2015-01-01

Proton therapy is an emerging technology for providing radiation therapy to cancer patients. The depth dose distribution of a proton beam makes it a preferable radiation modality as it reduces radiation to the healthy tissue outside the tumor, compared with conventional photon therapy. While theoretically beneficial, its clinical values are still being demonstrated from the increasing number of patients treated with proton therapy, from several dozen proton therapy centers around the world. High equipment and facility costs are often the major obstacle for its wider adoption. Because of the high cost and lack of definite clinical evidence of its superiority, proton therapy treatment faces criticism on its cost-effectiveness. Technological development is causing a gradual lowering of costs, and research and clinical studies are providing further evidence on its clinical utility. PMID:26604838

Material efficiency studies for a Compton camera designed to measure characteristic prompt gamma rays emitted during proton beam radiotherapy

PubMed Central

Robertson, Daniel; Polf, Jerimy C; Peterson, Steve W; Gillin, Michael T; Beddar, Sam

2011-01-01

Prompt gamma rays emitted from biological tissues during proton irradiation carry dosimetric and spectroscopic information that can assist with treatment verification and provide an indication of the biological response of the irradiated tissues. Compton cameras are capable of determining the origin and energy of gamma rays. However, prompt gamma monitoring during proton therapy requires new Compton camera designs that perform well at the high gamma energies produced when tissues are bombarded with therapeutic protons. In this study we optimize the materials and geometry of a three-stage Compton camera for prompt gamma detection and calculate the theoretical efficiency of such a detector. The materials evaluated in this study include germanium, bismuth germanate (BGO), NaI, xenon, silicon and lanthanum bromide (LaBr3). For each material, the dimensions of each detector stage were optimized to produce the maximum number of relevant interactions. These results were used to predict the efficiency of various multi-material cameras. The theoretical detection efficiencies of the most promising multi-material cameras were then calculated for the photons emitted from a tissue-equivalent phantom irradiated by therapeutic proton beams ranging from 50 to 250 MeV. The optimized detector stages had a lateral extent of 10 × 10 cm2 with the thickness of the initial two stages dependent on the detector material. The thickness of the third stage was fixed at 10 cm regardless of material. The most efficient single-material cameras were composed of germanium (3 cm) and BGO (2.5 cm). These cameras exhibited efficiencies of 1.15 × 10−4 and 9.58 × 10−5 per incident proton, respectively. The most efficient multi-material camera design consisted of two initial stages of germanium (3 cm) and a final stage of BGO, resulting in a theoretical efficiency of 1.26 × 10−4 per incident proton. PMID:21508442

Optimized magnet for a 250 MeV proton radiotherapy cyclotron

NASA Astrophysics Data System (ADS)

Kim, J.; Blosser, H.

2001-12-01

The NSCL accelerator group in 1993 carried out an extensive design study [1] for a K250 superconducting cyclotron for advanced cancer therapy. A private company ACCEL now offers cyclotrons based on this study on a commercial basis, and actual construction of a first such cyclotron is likely in the near future. In view of this, further optimization of the design of the superconducting magnet is currently underway. The configuration of the cyclotron has many similarities with previous NSCL-built superconducting cyclotrons—notable differences are the peak average field of 3 T (required by the focusing limit for protons) vs the 5 tesla of other MSU designs, and the use of four sectors rather than three to avoid the νr=3/2 stopband. The further optimization of the magnetic design described here keys on using the true 3D magnetic field program to more precisely match the design to an optimized orbital frequency configuration and to explore reducing the amount of spiral in the hills which then shortens the linear length of the rf elements and therefore reduces capacity and power consumption.

Protons -- The Future of Radiation Therapy?

NASA Astrophysics Data System (ADS)

Avery, Steven

2007-03-01

Cancer is the 2^nd highest cause of death in the United States. The challenges of controlling this disease remain more difficult as the population lives longer. Proton therapy offers another choice in the management of cancer care. Proton therapy has existed since the late 1950s and the first hospital based center in the United States opened in 1990. Since that time four hospital based proton centers are treating patients with other centers either under construction or under consideration. This talk will focus on an introduction to proton therapy: it's medical advantages over current treatment modalities, accelerators and beam delivery systems, applications to clinical radiation oncology and the future outlook for proton therapy.

A fast - Monte Carlo toolkit on GPU for treatment plan dose recalculation in proton therapy

NASA Astrophysics Data System (ADS)

Senzacqua, M.; Schiavi, A.; Patera, V.; Pioli, S.; Battistoni, G.; Ciocca, M.; Mairani, A.; Magro, G.; Molinelli, S.

2017-10-01

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement.

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy.

PubMed

Suzuki, Kazumichi; Palmer, Matthew B; Sahoo, Narayan; Zhang, Xiaodong; Poenisch, Falk; Mackin, Dennis S; Liu, Amy Y; Wu, Richard; Zhu, X Ronald; Frank, Steven J; Gillin, Michael T; Lee, Andrew K

2016-07-01

To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. The mean monthly equipment clinical availability for the spot scanning port in April 2012-March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012-August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for approximately 30%-40% of total treatment time for the total target volumes exceeding 200 cm(3), which was the case for more than 80% of the patients in this study. When total treatment time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation time, beam delivery time, and patient immobilization and setup time. The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling.

Quantitative proton imaging from multiple physics processes: a proof of concept

NASA Astrophysics Data System (ADS)

Bopp, C.; Rescigno, R.; Rousseau, M.; Brasse, D.

2015-07-01

Proton imaging is developed in order to improve the accuracy of charged particle therapy treatment planning. It makes it possible to directly map the relative stopping powers of the materials using the information on the energy loss of the protons. In order to reach a satisfactory spatial resolution in the reconstructed images, the position and direction of each particle is recorded upstream and downstream from the patient. As a consequence of individual proton detection, information on the transmission rate and scattering of the protons is available. Image reconstruction processes are proposed to make use of this information. A proton tomographic acquisition of an anthropomorphic head phantom was simulated. The transmission rate of the particles was used to reconstruct a map of the macroscopic cross section for nuclear interactions of the materials. A two-step iterative reconstruction process was implemented to reconstruct a map of the inverse scattering length of the materials using the scattering of the protons. Results indicate that, while the reconstruction processes should be optimized, it is possible to extract quantitative information from the transmission rate and scattering of the protons. This suggests that proton imaging could provide additional knowledge on the materials that may be of use to further improve treatment planning.

Quantitative proton imaging from multiple physics processes: a proof of concept.

PubMed

Bopp, C; Rescigno, R; Rousseau, M; Brasse, D

2015-07-07

Proton imaging is developed in order to improve the accuracy of charged particle therapy treatment planning. It makes it possible to directly map the relative stopping powers of the materials using the information on the energy loss of the protons. In order to reach a satisfactory spatial resolution in the reconstructed images, the position and direction of each particle is recorded upstream and downstream from the patient. As a consequence of individual proton detection, information on the transmission rate and scattering of the protons is available. Image reconstruction processes are proposed to make use of this information. A proton tomographic acquisition of an anthropomorphic head phantom was simulated. The transmission rate of the particles was used to reconstruct a map of the macroscopic cross section for nuclear interactions of the materials. A two-step iterative reconstruction process was implemented to reconstruct a map of the inverse scattering length of the materials using the scattering of the protons. Results indicate that, while the reconstruction processes should be optimized, it is possible to extract quantitative information from the transmission rate and scattering of the protons. This suggests that proton imaging could provide additional knowledge on the materials that may be of use to further improve treatment planning.

Advancing Cancer Treatment Delivery - Role of Physics

NASA Astrophysics Data System (ADS)

Bortfeld, Thomas

Radiation treatment of localized tumors has evolved rapidly in recent decades, allowing radiation oncologists to deliver more focused treatments with significantly reduced side effects. One of the disruptive innovations led by physicists has been the development of intensity-modulated and image-guided radiation therapy (IMRT and IGRT), which has become the state of the art in radiation therapy with photons. At the next stage of the development, there is now growing interest in treating tumors with protons or heavier particles, which have the added physical benefit of the Bragg peak. However, proton and heavier particle therapy is available to fewer than 1% of the patients. The first reason for that is the higher cost and bigger size of particle therapy facilities. The second reason is uncertainty of the treatment delivery, which limits its accuracy and precision. To address the first point (higher cost), physicists are involved in developments to make the equipment much more compact and cheaper. Examples include superconducting accelerators, laser-accelerated accelerators, more compact ``gantries'' that rotate the beam around the patient, as well as other solutions to treat the patients form multiple directions of incidence. The uncertainties in positioning the Bragg peak in the patient are being addressed by in-vivo measurements of dose deposition, or surrogates thereof. Examples include the measurement of prompt gamma radiation produced by the proton beam as it traverses the patient. Positron-Emission-Tomography (PET) scans have also been used to measure the tissue activation by the proton beam. Finally, the measurement of sound waves produced by pulsed proton beams leading to rapid expansions of the irradiated tissue has recently been successfully pursued. After resolving the issue of aiming a treatment beam with high precision and low cost, such that the majority of the patients will benefit from it, one of the next challenges for physicists in medicine is to better identify the actual target of the treatment, and the dynamics of treating it optimally in a multi-modality approach.

Proton therapy in the clinic.

PubMed

DeLaney, Thomas F

2011-01-01

The clinical advantage for proton radiotherapy over photon approaches is the marked reduction in integral dose to the patient, due to the absence of exit dose beyond the proton Bragg peak. The integral dose with protons is approximately 60% lower than that with any external beam photon technique. Pediatric patients, because of their developing normal tissues and anticipated length of remaining life, are likely to have the maximum clinical gain with the use of protons. Proton therapy may also allow treatment of some adult tumors to much more effective doses, because of normal tissue sparing distal to the tumor. Currently, the most commonly available proton treatment technology uses 3D conformal approaches based on (a) distal range modulation, (b) passive scattering of the proton beam in its x- and y-axes, and (c) lateral beam-shaping. It is anticipated that magnetic pencil beam scanning will become the dominant mode of proton delivery in the future, which will lower neutron scatter associated with passively scattered beam lines, reduce the need for expensive beam-shaping devices, and allow intensity-modulated proton radiotherapy. Proton treatment plans are more sensitive to variations in tumor size and normal tissue changes over the course of treatment than photon plans, and it is expected that adaptive radiation therapy will be increasingly important for proton therapy as well. While impressive treatment results have been reported with protons, their cost is higher than for photon IMRT. Hence, protons should ideally be employed for anatomic sites and tumors not well treated with photons. While protons appear cost-effective for pediatric tumors, their cost-effectiveness for treatment of some adult tumors, such as prostate cancer, is uncertain. Comparative studies have been proposed or are in progress to more rigorously assess their value for a variety of sites. The utility of proton therapy will be enhanced by technological developments that reduce its cost. Combinations of 3D protons with IMRT photons may offer improved treatment plans at lower cost than pure proton plans. Hypofractionation with proton therapy appears to be safe and cost-effective for many tumor sites, such as for selected liver, lung and pancreas cancers, and may yield significant reduction in the cost of a therapy course. Together, these offer practical strategies for expanding the clinical availability of proton therapy. Copyright © 2011 S. Karger AG, Basel.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bekelman, Justin E., E-mail: bekelman@uphs.upenn.edu; Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania

Purpose: To present the principles and rationale of the Proton Priority System (PROPS), a priority points framework that assigns higher scores to patients thought to more likely benefit from proton therapy, and the distribution of PROPS scores by patient characteristics Methods and Materials: We performed multivariable logistic regression to evaluate the association between PROPS scores and receipt of proton therapy, adjusted for insurance status, gender, race, geography, and the domains that inform the PROPS score. Results: Among 1529 adult patients considered for proton therapy prioritization during our Center's ramp-up phase of treatment availability, PROPS scores varied by age, diagnosis, site,more » and other PROPS domains. In adjusted analyses, receipt of proton therapy was lower for patients with non-Medicare relative to Medicare health insurance (commercial vs Medicare: adjusted odds ratio [OR] 0.47, 95% confidence interval [CI] 0.34-0.64; managed care vs Medicare: OR 0.40, 95% CI 0.28-0.56; Medicaid vs Medicare: OR 0.24, 95% CI 0.13-0.44). Proton Priority System score and age were not significantly associated with receipt of proton therapy. Conclusions: The Proton Priority System is a rationally designed and transparent system for allocation of proton therapy slots based on the best available evidence and expert opinion. Because the actual allocation of treatment slots depends mostly on insurance status, payers may consider incorporating PROPS, or its underlying principles, into proton therapy coverage policies.« less

Application of proton boron fusion reaction to radiation therapy: A Monte Carlo simulation study

NASA Astrophysics Data System (ADS)

Yoon, Do-Kun; Jung, Joo-Young; Suh, Tae Suk

2014-12-01

Three alpha particles are emitted from the point of reaction between a proton and boron. The alpha particles are effective in inducing the death of a tumor cell. After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton's maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here, we show that the effectiveness of the proton boron fusion therapy was verified using Monte Carlo simulations. We found that a dramatic increase by more than half of the proton's maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton's maximum dose point was located within the boron uptake region. In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.

SU-F-T-201: Acceleration of Dose Optimization Process Using Dual-Loop Optimization Technique for Spot Scanning Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirayama, S; Fujimoto, R

Purpose: The purpose was to demonstrate a developed acceleration technique of dose optimization and to investigate its applicability to the optimization process in a treatment planning system (TPS) for proton therapy. Methods: In the developed technique, the dose matrix is divided into two parts, main and halo, based on beam sizes. The boundary of the two parts is varied depending on the beam energy and water equivalent depth by utilizing the beam size as a singular threshold parameter. The optimization is executed with two levels of iterations. In the inner loop, doses from the main part are updated, whereas dosesmore » from the halo part remain constant. In the outer loop, the doses from the halo part are recalculated. We implemented this technique to the optimization process in the TPS and investigated the dependence on the target volume of the speedup effect and applicability to the worst-case optimization (WCO) in benchmarks. Results: We created irradiation plans for various cubic targets and measured the optimization time varying the target volume. The speedup effect was improved as the target volume increased, and the calculation speed increased by a factor of six for a 1000 cm3 target. An IMPT plan for the RTOG benchmark phantom was created in consideration of ±3.5% range uncertainties using the WCO. Beams were irradiated at 0, 45, and 315 degrees. The target’s prescribed dose and OAR’s Dmax were set to 3 Gy and 1.5 Gy, respectively. Using the developed technique, the calculation speed increased by a factor of 1.5. Meanwhile, no significant difference in the calculated DVHs was found before and after incorporating the technique into the WCO. Conclusion: The developed technique could be adapted to the TPS’s optimization. The technique was effective particularly for large target cases.« less

Assessment and improvements of Geant4 hadronic models in the context of prompt-gamma hadrontherapy monitoring

NASA Astrophysics Data System (ADS)

Dedes, G.; Pinto, M.; Dauvergne, D.; Freud, N.; Krimmer, J.; Létang, J. M.; Ray, C.; Testa, E.

2014-04-01

Monte Carlo simulations are nowadays essential tools for a wide range of research topics in the field of radiotherapy. They also play an important role in the effort to develop a real-time monitoring system for quality assurance in proton and carbon ion therapy, by means of prompt-gamma detection. The internal theoretical nuclear models of Monte Carlo simulation toolkits are of decisive importance for the accurate description of neutral or charged particle emission, produced by nuclear interactions between beam particles and target nuclei. We assess the performance of Geant4 nuclear models in the context of prompt-gamma emission, comparing them with experimental data from proton and carbon ion beams. As has been shown in the past and further indicated in our study, the prompt-gamma yields are consistently overestimated by Geant4 by a factor of about 100% to 200% over an energy range from 80 to 310 MeV/u for the case of 12C, and to a lesser extent for 160 MeV protons. Furthermore, we focus on the quantum molecular dynamics (QMD) modeling of ion-ion collisions, in order to optimize its description of light nuclei, which are abundant in the human body and mainly anticipated in hadrontherapy applications. The optimization has been performed by benchmarking QMD free parameters with well established nuclear properties. In addition, we study the effect of this optimization on charged particle emission. With the usage of the proposed parameter values, discrepancies reduce to less than 70%, with the highest values being attributed to the nucleon-ion induced prompt-gammas. This conclusion, also confirmed by the disagreement we observe in the case of proton beams, indicates the need for further investigation on nuclear models which describe proton and neutron induced nuclear reactions.

Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism and management

PubMed Central

Lv, Han-Jing; Qiu, Zhong-Min

2015-01-01

Refractory chronic cough due to gastroesophageal reflux is a troublesome condition unresponsive to the standard medical anti-reflux therapy. Its underlying mechanisms may include incomplete acid suppression, non-acid reflux, transient lower esophageal sphincter relaxations and esophageal hypersensitivity. The diagnosis of this disorder depends on both the findings of multi-channel intraluminal impedance-pH monitoring and the subsequent intensified anti-reflux therapy. The strategies of pharmacological treatment for refractory chronic cough due to reflux include the optimization of proton pump inhibitors and add-on therapies with histamine H2 receptor antagonists, baclofen and gabapentin. However, the further study is needed to satisfy its management. PMID:26413488

Reirradiation of head and neck cancer using modern highly conformal techniques.

PubMed

Ho, Jennifer C; Phan, Jack

2018-04-23

Locoregional disease recurrence or development of a second primary cancer after definitive radiotherapy for head and neck cancers remains a treatment challenge. Reirradiation utilizing traditional techniques has been limited by concern for serious toxicity. With the advent of newer, more precise radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT), proton radiotherapy, and stereotactic body radiotherapy (SBRT), there has been renewed interest in curative-intent head and neck reirradiation. However, as most studies were retrospective, single-institutional experiences, the optimal modality is not clear. We provide a comprehensive review of the outcomes of relevant studies using these 3 head and neck reirradiation techniques, followed by an analysis and comparison of the toxicity, tumor control, concurrent systemic therapy, and prognostic factors. Overall, there is evidence that IMRT, proton therapy, and SBRT reirradiation are feasible treatment options that offer a chance for durable local control and survival. Prospective studies, particularly randomized trials, are needed. © 2018 Wiley Periodicals, Inc.

Positioning of head and neck patients for proton therapy using proton range probes: a proof of concept study

NASA Astrophysics Data System (ADS)

Hammi, A.; Placidi, L.; Weber, D. C.; Lomax, A. J.

2018-01-01

To exploit the full potential of proton therapy, accurate and on-line methods to verify the patient positioning and the proton range during the treatment are desirable. Here we propose and validate an innovative technique for determining patient misalignment uncertainties through the use of a small number of low dose, carefully selected proton pencil beams (‘range probes’) (RP) with sufficient energy that their residual Bragg peak (BP) position and shape can be measured on exit. Since any change of the patient orientation in relation to these beams will result in changes of the density heterogeneities through which they pass, our hypothesis is that patient misalignments can be deduced from measured changes in Bragg curve (BC) shape and range. As such, a simple and robust methodology has been developed that estimates average proton range and range dilution of the detected residual BC, in order to locate range probe positions with optimal prediction power for detecting misalignments. The validation of this RP based approach has been split into two phases. First we retrospectively investigate its potential to detect translational patient misalignments under real clinical conditions. Second, we test it for determining rotational errors of an anthropomorphic phantom that was systematically rotated using an in-house developed high precision motion stage. Simulations of RPs in these two scenarios show that this approach could potentially predict translational errors to lower than1.5 mm and rotational errors to smaller than 1° using only three or five RPs positions respectively.

Feasibility study of using laser-generated neutron beam for BNCT.

PubMed

Kasesaz, Y; Rahmani, F; Khalafi, H

2015-09-01

The feasibility of using a laser-accelerated proton beam to produce a neutron source, via (p,n) reaction, for Boron Neutron Capture Therapy (BNCT) applications has been studied by MCNPX Monte Carlo code. After optimization of the target material and its thickness, a Beam Shaping Assembly (BSA) has been designed and optimized to provide appropriate neutron beam according to the recommended criteria by International Atomic Energy Agency. It was found that the considered laser-accelerated proton beam can provide epithermal neutron flux of ∼2×10(6) n/cm(2) shot. To achieve an appropriate epithermal neutron flux for BNCT treatment, the laser must operate at repetition rates of 1 kHz, which is rather ambitious at this moment. But it can be used in some BNCT researches field such as biological research. Copyright © 2015 Elsevier Ltd. All rights reserved.

"Radiobiology of Proton Therapy": Results of an international expert workshop.

PubMed

Lühr, Armin; von Neubeck, Cläre; Pawelke, Jörg; Seidlitz, Annekatrin; Peitzsch, Claudia; Bentzen, Søren M; Bortfeld, Thomas; Debus, Jürgen; Deutsch, Eric; Langendijk, Johannes A; Loeffler, Jay S; Mohan, Radhe; Scholz, Michael; Sørensen, Brita S; Weber, Damien C; Baumann, Michael; Krause, Mechthild

2018-05-31

The physical properties of proton beams offer the potential to reduce toxicity in tumor-adjacent normal tissues. Toward this end, the number of proton radiotherapy facilities has steeply increased over the last 10-15 years to currently around 70 operational centers worldwide. However, taking full advantage of the opportunities offered by proton radiation for clinical radiotherapy requires a better understanding of the radiobiological effects of protons alone or combined with drugs or immunotherapy on normal tissues and tumors. This report summarizes the main results of the international expert workshop "Radiobiology of Proton Therapy" that was held in November 2016 in Dresden. It addresses the major topics (1) relative biological effectiveness (RBE) in proton beam therapy, (2) interaction of proton radiobiology with radiation physics in current treatment planning, (3) biological effects in proton therapy combined with systemic treatments, and (4) testing biological effects of protons in clinical trials. Finally, important research avenues for improvement of proton radiotherapy based on radiobiological knowledge are identified. The clinical distribution of radiobiological effectiveness of protons alone or in combination with systemic chemo- or immunotherapies as well as patient stratification based on biomarker expressions are key to reach the full potential of proton beam therapy. Dedicated preclinical experiments, innovative clinical trial designs, and large high-quality data repositories will be most important to achieve this goal. Copyright © 2018 Elsevier B.V. All rights reserved.

Design and implementation of a robust and cost-effective double-scattering system at a horizontal proton beamline

NASA Astrophysics Data System (ADS)

Helmbrecht, S.; Baumann, M.; Enghardt, W.; Fiedler, F.; Krause, M.; Lühr, A.

2016-11-01

Purpose: particle therapy has the potential to improve radiooncology. With more and more facilities coming into operation, also the interest for research at proton beams increases. Though many centers provide beam at an experimental room, some of them do not feature a device for radiation field shaping, a so called nozzle. Therefore, a robust and cost-effective double-scattering system for horizontal proton beamlines has been designed and implemented. Materials and methods: the nozzle is based on the double scattering technique. Two lead scatterers, an aluminum ridge-filter and two brass collimators were optimized in a simulation study to form a laterally homogeneous 10 cm × 10 cm field with a spread-out Bragg-peak (SOBP). The parts were mainly manufactured using 3D printing techniques and the system was set up at OncoRay's experimental beamline. Measurement of the radiation field were carried out using a water phantom. Results: high levels of dose homogeneity were found in lateral (dose variation ΔD/D < ±2%) as well as in beam direction (ΔD/D < ± 3% in the SOBP). The system has already been used for radiobiology and physical experiments. Conclusion: the presented setup allows for creating clinically realistic extended radiation fields at fixed horizontal proton beamlines and is ready to use for internal and external users. The excellent performance combined with the simplistic design let it appear as a valuable option for proton therapy centers intending to foster their experimental portfolio.

Proton Radiation Therapy for Head and Neck Cancer: A Review of the Clinical Experience to Date

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holliday, Emma B.; Frank, Steven J., E-mail: sjfrank@mdanderson.org

2014-06-01

Proton beam radiation has been used for cancer treatment since the 1950s, but recent increasing interest in this form of therapy and the construction of hospital-based and clinic-based facilities for its delivery have greatly increased both the number of patients and the variety of tumors being treated with proton therapy. The mass of proton particles and their unique physical properties (ie, the Bragg peak) allow proton therapy to spare normal tissues distal to the tumor target from incidental irradiation. Initial observations show that proton therapy is particularly useful for treating tumors in challenging locations close to nontarget critical structures. Specifically,more » improvements in local control outcomes for patients with chordoma, chonodrosarcoma, and tumors in the sinonasal regions have been reported in series using proton. Improved local control and survival outcomes for patients with cancer of the head and neck region have also been seen with the advent of improvements in better imaging and multimodality therapy comprising surgery, radiation therapy, and chemotherapy. However, aggressive local therapy in the proximity of critical normal structures to tumors in the head and neck region may produce debilitating early and late toxic effects. Great interest has been expressed in evaluating whether proton therapy can improve outcomes, especially early and late toxicity, when used in the treatment of head and neck malignancies. This review summarizes the progress made to date in addressing this question.« less

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mishra, Mark V., E-mail: mmishra@umm.edu; Aggarwal, Sameer; Bentzen, Soren M.

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. Methods and Materials: Active PBT clinical trials were identified from (clinicaltrials.gov) and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% ofmore » trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.« less

Sparsity constrained split feasibility for dose-volume constraints in inverse planning of intensity-modulated photon or proton therapy

NASA Astrophysics Data System (ADS)

Penfold, Scott; Zalas, Rafał; Casiraghi, Margherita; Brooke, Mark; Censor, Yair; Schulte, Reinhard

2017-05-01

A split feasibility formulation for the inverse problem of intensity-modulated radiation therapy treatment planning with dose-volume constraints included in the planning algorithm is presented. It involves a new type of sparsity constraint that enables the inclusion of a percentage-violation constraint in the model problem and its handling by continuous (as opposed to integer) methods. We propose an iterative algorithmic framework for solving such a problem by applying the feasibility-seeking CQ-algorithm of Byrne combined with the automatic relaxation method that uses cyclic projections. Detailed implementation instructions are furnished. Functionality of the algorithm was demonstrated through the creation of an intensity-modulated proton therapy plan for a simple 2D C-shaped geometry and also for a realistic base-of-skull chordoma treatment site. Monte Carlo simulations of proton pencil beams of varying energy were conducted to obtain dose distributions for the 2D test case. A research release of the Pinnacle 3 proton treatment planning system was used to extract pencil beam doses for a clinical base-of-skull chordoma case. In both cases the beamlet doses were calculated to satisfy dose-volume constraints according to our new algorithm. Examination of the dose-volume histograms following inverse planning with our algorithm demonstrated that it performed as intended. The application of our proposed algorithm to dose-volume constraint inverse planning was successfully demonstrated. Comparison with optimized dose distributions from the research release of the Pinnacle 3 treatment planning system showed the algorithm could achieve equivalent or superior results.

Proton Radiotherapy for Childhood Ependymoma: Initial Clinical Outcomes and Dose Comparisons

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, Shannon M.; Safai, Sairos; Trofimov, Alexei

2008-07-15

Purpose: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients. Methods and Materials: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial andmore » supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared. Results: At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures. Conclusions: Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.« less

[Dosimetric comparing between protons beam and photons beam
for lung cancer radiotherapy: a meta-analysis].

PubMed

Tian, Guangwei; Li, Nan; Li, Guang

2013-05-01

The clinical evidences are not sufficient on the proton beam therapy of lung cancer for lacking of the RCTs on the comparing the proton with the photon beam in lung cancer radiotherapy. The aim of this study is to evaluate the dosimetry superiority of the proton beam and provide more valuable evidences to the clinical researches. Clinical trails of dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy were obtained from the Cochrane library, Pubmed, EMbase, CBM, CNKI, VIP, and Wan Fang databases. The data included in the study were evaluated and analyzed using the Cochrane Collaboration's RevMan 5.2 software. Six trails were included. Compared to photon therapy (three-dimensional conformal photon radiotherapy, 3D-CRT), the proton therapy had a significantly lower total lung Dmean (MD=-4.15, 95%CI: -5.56--2.74, P<0.001) and V20, V10, V5 (MD=-10.92, 95%CI: -13.23--8.62, P<0.001); The V20, V10, V5 significantly decreased in proton therapy group. Compared to photon therapy (intensity-modulated photon radiotherapy, IMRT), V20, V10, V5 were also significantly lowered in proton therapy group (MD=-3.70, 95%CI: -5.31--2.10, P<0.001; MD=-8.86, 95%CI: -10.74--6.98, P<0.001; MD=-20.13, 95%CI: -27.11--13.14, P<0.001); The esophagus Dmean was not lowered, while the heart Dmean decreased in proton therapy group. Comparing to photon beam radiotherapy (3D-CRT and IMRT), proton beam therapy is advantageous in dosimetry of the lung cancer radiotherapy and recommended for clinical applying.

Secondary radiation measurements for particle therapy applications: nuclear fragmentation produced by 4He ion beams in a PMMA target.

PubMed

Marafini, M; Paramatti, R; Pinci, D; Battistoni, G; Collamati, F; De Lucia, E; Faccini, R; Frallicciardi, P M; Mancini-Terracciano, C; Mattei, I; Muraro, S; Piersanti, L; Rovituso, M; Rucinski, A; Russomando, A; Sarti, A; Sciubba, A; Solfaroli Camillocci, E; Toppi, M; Traini, G; Voena, C; Patera, V

2017-02-21

Nowadays there is a growing interest in particle therapy treatments exploiting light ion beams against tumors due to their enhanced relative biological effectiveness and high space selectivity. In particular promising results are obtained by the use of 4 He projectiles. Unlike the treatments performed using protons, the beam ions can undergo a fragmentation process when interacting with the atomic nuclei in the patient body. In this paper the results of measurements performed at the Heidelberg Ion-Beam Therapy center are reported. For the first time the absolute fluxes and the energy spectra of the fragments-protons, deuterons, and tritons-produced by 4 He ion beams of 102, 125 and 145 MeV u -1 energies on a poly-methyl methacrylate target were evaluated at different angles. The obtained results are particularly relevant in view of the necessary optimization and review of the treatment planning software being developed for clinical use of 4 He beams in clinical routine and the relative bench-marking of Monte Carlo algorithm predictions.

Innovative thin silicon detectors for monitoring of therapeutic proton beams: preliminary beam tests

NASA Astrophysics Data System (ADS)

Vignati, A.; Monaco, V.; Attili, A.; Cartiglia, N.; Donetti, M.; Fadavi Mazinani, M.; Fausti, F.; Ferrero, M.; Giordanengo, S.; Hammad Ali, O.; Mandurrino, M.; Manganaro, L.; Mazza, G.; Sacchi, R.; Sola, V.; Staiano, A.; Cirio, R.; Boscardin, M.; Paternoster, G.; Ficorella, F.

2017-12-01

To fully exploit the physics potentials of particle therapy in delivering dose with high accuracy and selectivity, charged particle therapy needs further improvement. To this scope, a multidisciplinary project (MoVeIT) of the Italian National Institute for Nuclear Physics (INFN) aims at translating research in charged particle therapy into clinical outcome. New models in the treatment planning system are being developed and validated, using dedicated devices for beam characterization and monitoring in radiobiological and clinical irradiations. Innovative silicon detectors with internal gain layer (LGAD) represent a promising option, overcoming the limits of currently used ionization chambers. Two devices are being developed: one to directly count individual protons at high rates, exploiting the large signal-to-noise ratio and fast collection time in small thicknesses (1 ns in 50 μm) of LGADs, the second to measure the beam energy with time-of-flight techniques, using LGADs optimized for excellent time resolutions (Ultra Fast Silicon Detectors, UFSDs). The preliminary results of first beam tests with therapeutic beam will be presented and discussed.

Secondary radiation measurements for particle therapy applications: nuclear fragmentation produced by 4He ion beams in a PMMA target

NASA Astrophysics Data System (ADS)

Marafini, M.; Paramatti, R.; Pinci, D.; Battistoni, G.; Collamati, F.; De Lucia, E.; Faccini, R.; Frallicciardi, P. M.; Mancini-Terracciano, C.; Mattei, I.; Muraro, S.; Piersanti, L.; Rovituso, M.; Rucinski, A.; Russomando, A.; Sarti, A.; Sciubba, A.; Solfaroli Camillocci, E.; Toppi, M.; Traini, G.; Voena, C.; Patera, V.

2017-02-01

Nowadays there is a growing interest in particle therapy treatments exploiting light ion beams against tumors due to their enhanced relative biological effectiveness and high space selectivity. In particular promising results are obtained by the use of 4He projectiles. Unlike the treatments performed using protons, the beam ions can undergo a fragmentation process when interacting with the atomic nuclei in the patient body. In this paper the results of measurements performed at the Heidelberg Ion-Beam Therapy center are reported. For the first time the absolute fluxes and the energy spectra of the fragments—protons, deuterons, and tritons—produced by 4He ion beams of 102, 125 and 145 MeV u-1 energies on a poly-methyl methacrylate target were evaluated at different angles. The obtained results are particularly relevant in view of the necessary optimization and review of the treatment planning software being developed for clinical use of 4He beams in clinical routine and the relative bench-marking of Monte Carlo algorithm predictions.

Development of a center for light ion therapy and accurate tumor diagnostics at karolinska institutet and hospital

NASA Astrophysics Data System (ADS)

Brahme, Anders; Lind, Bengt K.

2002-04-01

Radiation therapy is today in a state of very rapid development with new intensity modulated treatment techniques continuously being developed. This has made intensity modulated electron and photon beams almost as powerful as conventional uniform beam proton therapy. To be able to cure also the most advanced hypoxic and radiation resistant tumors of complex local spread, intensity modulated light ion beams are really the ultimate tool and only slightly more expensive than proton therapy. The aim of the new center for ion therapy and tumor diagnostics in Stockholm is to develop radiobiologically optimized 3-dimensional pencil beam scanning techniques. Beside the "classical" approaches using low ionization density hydrogen ions (protons, but also deuterons and tritium nuclei) and high ionization density carbon ions, two new approaches will be developed. In the first one lithium or beryllium ions, that induce the least detrimental biological effect to normal tissues for a given biological effect in a small volume of the tumor, will be key particles. In the second approach, referred patients will be given a high-dose high-precision "boost" treatment with carbon or oxygen ions during one week preceding the final treatment with conventional radiations in the referring hospital. The rationale behind these approaches is to reduce the high ionization density dose to the normal tissue stroma inside the tumor and to ensure a microscopically uniform dose delivery. The principal idea of the center is to closely integrate ion therapy into the clinical routine and research of a large radiotherapy department. The light ion therapy center will therefore be combined with advanced tumor diagnostics including MR and PET-CT imaging to facilitate efficient high-precision high-dose boost treatment of remitted patients. The possibility to do 3D tumor diagnostics and 3D dose delivery verification with the same PET camera will be the ultimate step in high quality adaptive radiation therapy where alterations in the delivered dose can be corrected by subsequent treatments

Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies

NASA Astrophysics Data System (ADS)

van de Water, Steven; Albertini, Francesca; Weber, Damien C.; Heijmen, Ben J. M.; Hoogeman, Mischa S.; Lomax, Antony J.

2018-01-01

The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 ‘synthetic’ CTs with varying nasal cavity filling. The robust optimization method available in our treatment planning system ‘Erasmus-iCycle’ was extended to also account for anatomical uncertainties by including (synthetic) CTs with varying patient anatomy as error scenarios in the inverse optimization. For each patient, we generated treatment plans using anatomical robust optimization and, for benchmarking, using SFUD optimization and online plan adaptation. Clinical target volume (CTV) and organ-at-risk (OAR) doses were assessed by recalculating the treatment plans on the synthetic CTs, evaluating dose distributions individually and accumulated over an entire fractionated 50 GyRBE treatment, assuming each synthetic CT to correspond to a 2 GyRBE fraction. Treatment plans were also evaluated using actual repeat CTs. Anatomical robust optimization resulted in adequate CTV doses (V95%  ⩾  98% and V107%  ⩽  2%) if at least three synthetic CTs were included in addition to the planning CT. These CTV requirements were also fulfilled for online plan adaptation, but not for the SFUD approach, even when applying a margin of 5 mm. Compared with anatomical robust optimization, OAR dose parameters for the accumulated dose distributions were on average 5.9 GyRBE (20%) higher when using SFUD optimization and on average 3.6 GyRBE (18%) lower for online plan adaptation. In conclusion, anatomical robust optimization effectively accounted for changes in nasal cavity filling during IMPT, providing substantially improved CTV and OAR doses compared with conventional SFUD optimization. OAR doses can be further reduced by using online plan adaptation.

Enhanced laser radiation pressure acceleration of protons with a gold cone-capillary

NASA Astrophysics Data System (ADS)

Lv, Chong; Xie, Bai-Song; Wan, Feng; Hou, Ya-Juan; Jia, Mo-Ran; Sang, Hai-Bo; Hong, Xue-Ren; Liu, Shi-Bing

2017-03-01

A scheme with a gold cone-capillary is proposed to improve the protons acceleration, and involved problems are investigated by using the two-dimensional particle-in-cell simulations. It is demonstrated that the cone-capillary can efficiently guide and collimate the protons to a longer distance and result in a better beam quality with a dense density ≥ 10 n c , monoenergetic peak energy E k ˜ 1.51 GeV , spatial emittance ˜ 0.0088 mm mrad with divergence angle θ ˜ 1.0 ° and diameter ˜ 0.5 μ m . The enhancement is mainly attributed to the focusing effect by the transverse electric field generated by the cone as well as the capillary, which can prevent greatly the protons from expanding in the transverse direction. Comparable to without the capillary, the protons energy spectra have a stable monoenergetic peak and divergence angle nearby 1.0 ° in longer time. Besides, the efficiency of acceleration depending on the capillary length is explored, and the optimal capillary length is also achieved. Such a target may be beneficial to many applications such as ion fast ignition in inertial fusion, proton therapy and so on.

SU-E-T-649: Quality Assurances for Proton Therapy Delivery Equipment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arjomandy, B; Kase, Y; Flanz, J

2015-06-15

Purpose: The number of proton therapy centers has increased dramatically over the past decade. Currently, there is no comprehensive set of guidelines that addresses quality assurance (QA) procedures for the different technologies used for proton therapy. The AAPM has charged task group 224 (TG-224) to provide recommendations for QA required for accurate and safe dose delivery, using existing and next generation proton therapy delivery equipment. Methods: A database comprised of QA procedures and tolerance limits was generated from many existing proton therapy centers in and outside of the US. These consist of proton therapy centers that possessed double scattering, uniformmore » scanning, and pencil beams delivery systems. The diversity in beam delivery systems as well as the existing devices to perform QA checks for different beam parameters is the main subject of TG-224. Based on current practice at the clinically active proton centers participating in this task group, consensus QA recommendations were developed. The methodologies and requirements of the parameters that must be verified for consistency of the performance of the proton beam delivery systems are discussed. Results: TG-224 provides procedures and QA checks for mechanical, imaging, safety and dosimetry requirements for different proton equipment. These procedures are categorized based on their importance and their required frequencies in order to deliver a safe and consistent dose. The task group provides daily, weekly, monthly, and annual QA check procedures with their tolerance limits. Conclusions: The procedures outlined in this protocol provide sufficient information to qualified medical physicists to perform QA checks for any proton delivery system. Execution of these procedures should provide confidence that proton therapy equipment is functioning as commissioned for patient treatment and delivers dose safely and accurately within the established tolerance limits. The report will be published in late 2015.« less

SU-F-T-207: Does the Greater Flexibility of Pencil Beam Scanning Reduce the Need for a Proton Gantry?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, S; Depauw, N; Flanz, J

2016-06-15

Purpose: Gantry-less proton treatment facility could lower the capital cost of proton therapy. This study investigates the dosimetric feasibility of using only coplanar pencil beam scanning (PBS) beams for those patients who had beam angles that would not have been deliverable without the gantry. Those coplanar beams are implemented on gantry-less horizontal beam-line with patients in sitting or standing positions. Methods: We have selected ten patients (seven head-and-neck, one thoracic, one abdominal and one pelvic case) with clinically delivered double scattering (DS) or PBS treatment plans with beam angles that were challenging to achieve without a gantry. After removing thesemore » beams angles, PBS plans were optimized for gantry-less intensity modulated proton therapy (IMPT) or single field optimization (SFO) with multi-criteria optimization (MCO). For head-and-neck patients who were treated by DS, we generated PBS plans with non-coplanar beams for comparison. Dose-volume-histograms (DVHs), target homogeneity index (HI), mean dose, D-2 and D-98 were reported. Robustness analysis was performed with ±2.5 mm setup errors and ±3.5% range uncertainties for three head-and-neck patients. Results: PBS-gantry-less plans provided more homogenous target coverage and significant improvements on organs-at-risk (OARs) sparing, compared to passive scattering treatments with a gantry. The PBS gantry-less treatments reduced the HI for target coverage by 1.3% to 47.2%, except for a suprasellar patient and a liver patient. The PBS-gantry-less plans reduced the D-mean of OARs by 3.6% to 67.4%. The PBS-gantry plans had similar target coverage and only marginal improvements on OAR sparing as compared to the PBS-gantry-less plans. These two PBS plans also had similar robustness relative to range uncertainties and setup errors. Conclusion: The gantry-less plans have with less mean dose to OARs and more homogeneous target coverage. Although the PBS-gantry plans have slightly improved target coverage and OARs sparing, the overall benefit of having a gantry to provide non-coplanar beams is debatable.« less

Beyond Gaussians: a study of single spot modeling for scanning proton dose calculation

PubMed Central

Li, Yupeng; Zhu, Ronald X.; Sahoo, Narayan; Anand, Aman; Zhang, Xiaodong

2013-01-01

Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field-size effects on dose output. In the present study, we developed a pencil-beam algorithm for scanning-proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil-beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field-size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy. PMID:22297324

Decision analytic modeling for the economic analysis of proton radiotherapy for non-small cell lung cancer

PubMed Central

Richard, Patrick J.; Zeng, Jing; Apisarnthanarax, Smith; Rengan, Ramesh; Phillips, Mark H.

2018-01-01

Background Although proton radiation treatments are more costly than photon/X-ray therapy, they may lower overall treatment costs through reducing rates of severe toxicities and the costly management of those toxicities. To study this issue, we created a decision-model comparing proton vs. X-ray radiotherapy for locally advanced non-small cell lung cancer patients. Methods An influence diagram was created to model for radiation delivery, associated 6-month pneumonitis/esophagitis rates, and overall costs (radiation plus toxicity costs). Pneumonitis (age, chemo type, V20, MLD) and esophagitis (V60) predictors were modeled to impact toxicity rates. We performed toxicity-adjusted, rate-adjusted, risk group-adjusted, and radiosensitivity analyses. Results Upfront proton treatment costs exceeded that of photons [$16,730.37 (3DCRT), $23,893.83 (IMRT), $41,061.80 (protons)]. Based upon expected population pneumonitis and esophagitis rates for each modality, protons would be expected to recover $1,065.62 and $1,139.63 of the cost difference compared to 3DCRT or IMRT. For patients treated with IMRT experiencing grade 4 pneumonitis or grade 4 esophagitis, costs exceeded patients treated with protons without this toxicity. 3DCRT patients with grade 4 esophagitis had higher costs than proton patients without this toxicity. For the risk group analysis, high risk patients (age >65, carboplatin/paclitaxel) benefited more from proton therapy. A biomarker may allow patient selection for proton therapy, although the AUC alone is not sufficient to determine if the biomarker is clinically useful. Conclusions The comparison between proton and photon/X-ray radiation therapy for NSCLC needs to consider both the up-front cost of treatment and the possible long term cost of complications. In our analysis, current costs favor X-ray therapy. However, relatively small reductions in the cost of proton therapy may result in a shift to the preference for proton therapy.

Feasibility of MRI-only treatment planning for proton therapy in brain and prostate cancers: Dose calculation accuracy in substitute CT images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koivula, Lauri

Purpose: Magnetic resonance imaging (MRI) is increasingly used for radiotherapy target delineation, image guidance, and treatment response monitoring. Recent studies have shown that an entire external x-ray radiotherapy treatment planning (RTP) workflow for brain tumor or prostate cancer patients based only on MRI reference images is feasible. This study aims to show that a MRI-only based RTP workflow is also feasible for proton beam therapy plans generated in MRI-based substitute computed tomography (sCT) images of the head and the pelvis. Methods: The sCTs were constructed for ten prostate cancer and ten brain tumor patients primarily by transforming the intensity valuesmore » of in-phase MR images to Hounsfield units (HUs) with a dual model HU conversion technique to enable heterogeneous tissue representation. HU conversion models for the pelvis were adopted from previous studies, further extended in this study also for head MRI by generating anatomical site-specific conversion models (a new training data set of ten other brain patients). This study also evaluated two other types of simplified sCT: dual bulk density (for bone and water) and homogeneous (water only). For every clinical case, intensity modulated proton therapy (IMPT) plans robustly optimized in standard planning CTs were calculated in sCT for evaluation, and vice versa. Overall dose agreement was evaluated using dose–volume histogram parameters and 3D gamma criteria. Results: In heterogeneous sCTs, the mean absolute errors in HUs were 34 (soft tissues: 13, bones: 92) and 42 (soft tissues: 9, bones: 97) in the head and in the pelvis, respectively. The maximum absolute dose differences relative to CT in the brain tumor clinical target volume (CTV) were 1.4% for heterogeneous sCT, 1.8% for dual bulk sCT, and 8.9% for homogenous sCT. The corresponding maximum differences in the prostate CTV were 0.6%, 1.2%, and 3.6%, respectively. The percentages of dose points in the head and pelvis passing 1% and 1 mm gamma index criteria were over 91%, 85%, and 38% with heterogeneous, dual bulk, and homogeneous sCTs, respectively. There were no significant changes to gamma index pass rates for IMPT plans first optimized in CT and then calculated in heterogeneous sCT versus IMPT plans first optimized in heterogeneous sCT and then calculated on standard CT. Conclusions: This study demonstrates that proton therapy dose calculations on heterogeneous sCTs are in good agreement with plans generated with standard planning CT. An MRI-only based RTP workflow is feasible in IMPT for brain tumors and prostate cancers.« less

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Kazumichi, E-mail: kazumichisuzuki@gmail.c

Purpose: To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. Methods: At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery systemmore » downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. Results: The mean monthly equipment clinical availability for the spot scanning port in April 2012–March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012–August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for approximately 30%–40% of total treatment time for the total target volumes exceeding 200 cm{sup 3}, which was the case for more than 80% of the patients in this study. When total treatment time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation time, beam delivery time, and patient immobilization and setup time. Conclusions: The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling.« less

Pre-treatment patient-specific stopping power by combining list-mode proton radiography and x-ray CT

NASA Astrophysics Data System (ADS)

Collins-Fekete, Charles-Antoine; Brousmiche, Sébastien; Hansen, David C.; Beaulieu, Luc; Seco, Joao

2017-09-01

The relative stopping power (RSP) uncertainty is the largest contributor to the range uncertainty in proton therapy. The purpose of this work was to develop a systematic method that yields accurate and patient-specific RSPs by combining (1) pre-treatment x-ray CT and (2) daily proton radiography of the patient. The method was formulated as a penalized least squares optimization problem (argmin(\\Vert {A}{x}-{b}\\Vert _22 )). The parameter A represents the cumulative path-length crossed by the proton in each material, separated by thresholding on the HU. The material RSPs (water equivalent thickness/physical thickness) are denoted by x. The parameter b is the list-mode proton radiography produced using Geant4 simulations. The problem was solved using a non-negative linear-solver with {x}≥slant0 . A was computed by superposing proton trajectories calculated with a cubic or linear spline approach to the CT. The material’s RSP assigned in Geant4 were used for reference while the clinical HU-RSP calibration curve was used for comparison. The Gammex RMI-467 phantom was first investigated. The standard deviation between the estimated material RSP and the calculated RSP is 0.45%. The robustness of the techniques was then assessed as a function of the number of projections and initial proton energy. Optimization with two initial projections yields precise RSP (⩽1.0%) for 330 MeV protons. 250 MeV protons have shown higher uncertainty (⩽2.0%) due to the loss of precision in the path estimate. Anthropomorphic phantoms of the head, pelvis, and lung were subsequently evaluated. Accurate RSP has been obtained for the head (μ =0.21+/-1.63% ), the lung (μ=0.06+/-0.99% ) and the pelvis (μ=0.90+/-3.87% ). The range precision has been optimized using the calibration curves obtained with the algorithm, yielding a mean R80 difference to the reference of 0.11  ±0.09%, 0.28  ±  0.34% and 0.05 +/- 0.06% in the same order. The solution’s accuracy is limited by the assumed HU/RSP bijection, neglecting inherent degeneracy. The proposed formulation of the problem with prior knowledge x-ray CT demonstrates potential to increase the accuracy of present RSP estimates.

Pre-treatment patient-specific stopping power by combining list-mode proton radiography and x-ray CT.

PubMed

Collins-Fekete, Charles-Antoine; Brousmiche, Sébastien; Hansen, David C; Beaulieu, Luc; Seco, Joao

2017-08-03

The relative stopping power (RSP) uncertainty is the largest contributor to the range uncertainty in proton therapy. The purpose of this work was to develop a systematic method that yields accurate and patient-specific RSPs by combining (1) pre-treatment x-ray CT and (2) daily proton radiography of the patient. The method was formulated as a penalized least squares optimization problem (argmin([Formula: see text])). The parameter A represents the cumulative path-length crossed by the proton in each material, separated by thresholding on the HU. The material RSPs (water equivalent thickness/physical thickness) are denoted by x. The parameter b is the list-mode proton radiography produced using Geant4 simulations. The problem was solved using a non-negative linear-solver with [Formula: see text]. A was computed by superposing proton trajectories calculated with a cubic or linear spline approach to the CT. The material's RSP assigned in Geant4 were used for reference while the clinical HU-RSP calibration curve was used for comparison. The Gammex RMI-467 phantom was first investigated. The standard deviation between the estimated material RSP and the calculated RSP is 0.45%. The robustness of the techniques was then assessed as a function of the number of projections and initial proton energy. Optimization with two initial projections yields precise RSP (⩽1.0%) for 330 MeV protons. 250 MeV protons have shown higher uncertainty (⩽2.0%) due to the loss of precision in the path estimate. Anthropomorphic phantoms of the head, pelvis, and lung were subsequently evaluated. Accurate RSP has been obtained for the head ([Formula: see text]), the lung ([Formula: see text]) and the pelvis ([Formula: see text]). The range precision has been optimized using the calibration curves obtained with the algorithm, yielding a mean [Formula: see text] difference to the reference of 0.11  ±0.09%, 0.28  ±  0.34% and [Formula: see text] in the same order. The solution's accuracy is limited by the assumed HU/RSP bijection, neglecting inherent degeneracy. The proposed formulation of the problem with prior knowledge x-ray CT demonstrates potential to increase the accuracy of present RSP estimates.

Treatment planning optimisation in proton therapy

PubMed Central

McGowan, S E; Burnet, N G; Lomax, A J

2013-01-01

ABSTRACT. The goal of radiotherapy is to achieve uniform target coverage while sparing normal tissue. In proton therapy, the same sources of geometric uncertainty are present as in conventional radiotherapy. However, an important and fundamental difference in proton therapy is that protons have a finite range, highly dependent on the electron density of the material they are traversing, resulting in a steep dose gradient at the distal edge of the Bragg peak. Therefore, an accurate knowledge of the sources and magnitudes of the uncertainties affecting the proton range is essential for producing plans which are robust to these uncertainties. This review describes the current knowledge of the geometric uncertainties and discusses their impact on proton dose plans. The need for patient-specific validation is essential and in cases of complex intensity-modulated proton therapy plans the use of a planning target volume (PTV) may fail to ensure coverage of the target. In cases where a PTV cannot be used, other methods of quantifying plan quality have been investigated. A promising option is to incorporate uncertainties directly into the optimisation algorithm. A further development is the inclusion of robustness into a multicriteria optimisation framework, allowing a multi-objective Pareto optimisation function to balance robustness and conformity. The question remains as to whether adaptive therapy can become an integral part of a proton therapy, to allow re-optimisation during the course of a patient's treatment. The challenge of ensuring that plans are robust to range uncertainties in proton therapy remains, although these methods can provide practical solutions. PMID:23255545

Rhabdomyosarcoma of the trachea: first reported case treated with proton beam therapy.

PubMed

Exley, R; Bernstein, J M; Brennan, B; Rothera, M P

2012-09-01

We report a case of rhabdomyosarcoma of the trachea in a 14-month-old child, and we present the first reported use of proton beam therapy for this tumour. A 14-month-old girl presented acutely with a seven-day history of biphasic stridor. Emergency endoscopic debulking of a posterior tracheal mass was undertaken. Histological examination revealed an embryonal rhabdomyosarcoma with anaplasia. Multimodality therapy with surgery and chemotherapy was administered in the UK, and proton beam therapy in the USA. Only three cases of rhabdomyosarcoma of the trachea have previously been reported in the world literature. This is the first reported case of treatment of this tumour with proton beam therapy. Compared with conventional radiotherapy, proton beam therapy may confer improved long-term outcome in children, with benefits including reduced irradiation of the spinal cord.

Development of a multi-knife-edge slit collimator for prompt gamma ray imaging during proton beam cancer therapy

NASA Astrophysics Data System (ADS)

Ready, John Francis, III

Proton beam usage to treat cancer has recently experienced rapid growth, as it offers the ability to target dose delivery in a patient more precisely than traditional x-ray treatment methods. Protons stop within the patient, delivering the maximum dose at the end of their track--a phenomenon described as the Bragg peak. However, because a large dose is delivered to a small volume, proton therapy is very sensitive to errors in patient setup and treatment planning calculations. Additionally, because all primary beam particles stop in the patient, there is no direct information available to verify dose delivery. These factors contribute to the range uncertainty in proton therapy, which ultimately hinders its clinical usefulness. A reliable method of proton range verification would allow the clinician to fully utilize the precise dose delivery of the Bragg peak. Several methods to verify proton range detect secondary emissions, especially prompt gamma ray (PG) emissions. However, detection of PGs is challenging due to their high energy (2-10 MeV) and low attenuation coefficients, which limit PG interactions in materials. Therefore, detection and collimation methods must be specifically designed for prompt gamma ray imaging (PGI) applications. In addition, production of PGs relies on delivering a dose of radiation to the patient. Ideally, verification of the Bragg peak location exposes patients to a minimal dose, thus limiting the PG counts available to the imaging system. An additional challenge for PGI is the lack of accurate simulation models, which limit the study of PG production characteristics and the relationship between PG distribution and dose delivery. Specific limitations include incorrect modeling of the reaction cross sections, gamma emission yields, and angular distribution of emission for specific photon energies. While simulations can still be valuable assets in designing a system to detect and image PGs, until new models are developed and incorporated into Monte Carlo simulation packages, simulations cannot be used to study the production and location of PG emissions during proton therapy. This work presents a novel system to image PGs emitted during proton therapy to verify proton beam range. The imaging system consists of a multi-slit collimator paired with a position-sensitive LSO scintillation detector. This innovative design is the first collimated imaging system to implement two-dimensional (2-D) imaging for PG proton beam range verification, while also providing a larger field of view than compared to single-slit collimator systems. Other, uncollimated imaging systems have been explored for PGI applications, such as Compton cameras. However, Compton camera designs are severely limited by counting rate capabilities. A recent Compton camera study reported count rate capability of about 5 kHz. However, at a typical clinical beam current of 1.0 nA, the estimated PG emission rate would be 6 x 108 per second. After accounting for distance to the detector and interaction efficiencies, the detection system will still be overwhelmed with counts in the MHz range, causing false coincidences and hindering the operation of the imaging system. Initial measurements using 50 MeV protons demonstrated the ability of our system to reconstruct 2-D PG distributions at clinical beam currents. A Bragg peak localization precision of 1 mm (2sigma) was achieved with delivery of (1.7 +/- 0.8) x 108 protons into a PMMA target, suggesting the ability of the system to detect relative shifts in proton range while delivering fewer protons than used in a typical treatment fraction. This is key, as the ideal system allows the clinician to verify proton range when delivering only a small portion of the prescribed dose, preventing the mistreatment of the patient. Additionally, the absolute position of the Bragg peak was identified to within 1.6 mm (2sigma) with 5.6 x 1010 protons delivered. These promising results warrant further investigation and system optimization for clinical implementation. While further measurements at clinical beam energy levels will be required to verify system performance, these preliminary results provide evidence that 2-D image reconstruction, with 1-2 mm accuracy, is possible with this design. Implementing such a system in the clinical setting would greatly improve proton therapy cancer treatment outcomes.

Pencil Beam Scanning Proton Therapy for Rhabdomyosarcoma of the Biliary Tract.

PubMed

Pater, Luke; Turpin, Brian; Mascia, Anthony

2017-10-05

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood with 250-350 cases diagnosed annually in the United States. Biliary tract rhabdomyosarcoma is rare, representing <1% of the RMS cases. Due to its location, resection is clinically challenging, and functional complications exist and persist from biliary obstruction. The anatomical location of this tumor presents both opportunities and challenges for pencil beam scanning proton therapy. Proton therapy offers a dosimetric and clinical advantage by sparing the healthy liver, stomach, contra-lateral kidney and bowel. Motion management and anatomical variations, such as intestinal filling or weight loss, requiring routine dosimetric evaluation and possible adaptive treatment planning, present challenges for the use of proton therapy. By taking advantage of the superior dose distribution of proton radiation, assessing the impact of tumor and anatomy motion, and performing regular dose evaluations, biliary tract RMS is an ideal diagnosis for pencil beam scanning proton therapy.

New superconducting cyclotron driven scanning proton therapy systems

NASA Astrophysics Data System (ADS)

Klein, Hans-Udo; Baumgarten, Christian; Geisler, Andreas; Heese, Jürgen; Hobl, Achim; Krischel, Detlef; Schillo, Michael; Schmidt, Stefan; Timmer, Jan

2005-12-01

Since one and a half decades ACCEL is investing in development and engineering of state of the art particle-therapy systems. A new medical superconducting 250 MeV proton cyclotron with special focus on the present and future beam requirements of fast scanning treatment systems has been designed. The first new ACCEL medical proton cyclotron is under commissioning at PSI for their PROSCAN proton therapy facility having undergone successful factory tests especially of the closed loop cryomagnetic system. The second cyclotron is part of ACCEL's integrated proton therapy system for Europe's first clinical center, RPTC in Munich. The cyclotron, the energy selection system, the beamline as well as the four gantries and patient positioners have been installed. The scanning system and major parts of the control software have already been tested. We will report on the concept of ACCEL's superconducting cyclotron driven scanning proton therapy systems and the current status of the commissioning work at PSI and RPTC.

Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, Romaine C., E-mail: rnichols@floridaproton.org; Huh, Soon N.; Prado, Karl L.

2012-05-01

Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of themore » target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.« less

Protons offer reduced normal-tissue exposure for patients receiving postoperative radiotherapy for resected pancreatic head cancer.

PubMed

Nichols, Romaine C; Huh, Soon N; Prado, Karl L; Yi, Byong Y; Sharma, Navesh K; Ho, Meng W; Hoppe, Bradford S; Mendenhall, Nancy P; Li, Zuofeng; Regine, William F

2012-05-01

To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting. Copyright © 2012 Elsevier Inc. All rights reserved.

Shielding implications for secondary neutrons and photons produced within the patient during IMPT.

PubMed

DeMarco, J; Kupelian, P; Santhanam, A; Low, D

2013-07-01

Intensity modulated proton therapy (IMPT) uses a combination of computer controlled spot scanning and spot-weight optimized planning to irradiate the tumor volume uniformly. In contrast to passive scattering systems, secondary neutrons and photons produced from inelastic proton interactions within the patient represent the major source of emitted radiation during IMPT delivery. Various published studies evaluated the shielding considerations for passive scattering systems but did not directly address secondary neutron production from IMPT and the ambient dose equivalent on surrounding occupational and nonoccupational work areas. Thus, the purpose of this study was to utilize Monte Carlo simulations to evaluate the energy and angular distributions of secondary neutrons and photons following inelastic proton interactions within a tissue-equivalent phantom for incident proton spot energies between 70 and 250 MeV. Monte Carlo simulation methods were used to calculate the ambient dose equivalent of secondary neutrons and photons produced from inelastic proton interactions in a tissue-equivalent phantom. The angular distribution of emitted neutrons and photons were scored as a function of incident proton energy throughout a spherical annulus at 1, 2, 3, 4, and 5 m from the phantom center. Appropriate dose equivalent conversion factors were applied to estimate the total ambient dose equivalent from secondary neutrons and photons. A reference distance of 1 m from the center of the patient was used to evaluate the mean energy distribution of secondary neutrons and photons and the resulting ambient dose equivalent. For an incident proton spot energy of 250 MeV, the total ambient dose equivalent (3.6 × 10(-3) mSv per proton Gy) was greatest along the direction of the incident proton spot (0°-10°) with a mean secondary neutron energy of 71.3 MeV. The dose equivalent decreased by a factor of 5 in the backward direction (170°-180°) with a mean energy of 4.4 MeV. An 8 × 8 × 8 cm(3) volumetric spot distribution (5 mm FWHM spot size, 4 mm spot spacing) optimized to produce a uniform dose distribution results in an ambient dose equivalent of 4.5 × 10(-2) mSv per proton Gy in the forward direction. This work evaluated the secondary neutron and photon emission due to monoenergetic proton spots between 70 and 250 MeV, incident on a tissue equivalent phantom. Example calculations were performed to estimate concrete shield thickness based upon appropriate workload and shielding design assumptions. Although lower than traditional passive scattered proton therapy systems, the ambient dose equivalent from secondary neutrons produced by the patient during IMPT can be significant relative to occupational and nonoccupational workers in the vicinity of the treatment vault. This work demonstrates that Monte Carlo simulations are useful as an initial planning tool for studying the impact of the treatment room and maze design on surrounding occupational and nonoccupational work areas.

Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy.

PubMed

Sengbusch, E; Pérez-Andújar, A; DeLuca, P M; Mackie, T R

2009-02-01

Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180 degrees continuous arc proton therapy and for 180 degrees split arc proton therapy (two 90 degrees arcs) using CT# profiles from the Pinnacle (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the proton kinetic energy from 250 to 200 MeV decreases the total neutron energy fluence produced by stopping a monoenergetic pencil beam in a water phantom by a factor of 2.3. It is possible to significantly lower the requirements on the maximum kinetic energy of a compact proton accelerator if the ability to treat a small percentage of patients with rotational therapy is sacrificed. This decrease in maximum kinetic energy, along with the corresponding decrease in neutron production, could lower the cost and ease the engineering constraints on a compact proton accelerator treatment facility.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

PubMed Central

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled. PMID:23635256

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

PubMed

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PubMed

Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

2016-11-01

To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Proton and helium ion radiotherapy for meningioma tumors: a Monte Carlo-based treatment planning comparison.

PubMed

Tessonnier, Thomas; Mairani, Andrea; Chen, Wenjing; Sala, Paola; Cerutti, Francesco; Ferrari, Alfredo; Haberer, Thomas; Debus, Jürgen; Parodi, Katia

2018-01-09

Due to their favorable physical and biological properties, helium ion beams are increasingly considered a promising alternative to proton beams for radiation therapy. Hence, this work aims at comparing in-silico the treatment of brain and ocular meningiomas with protons and helium ions, using for the first time a dedicated Monte Carlo (MC) based treatment planning engine (MCTP) thoroughly validated both in terms of physical and biological models. Starting from clinical treatment plans of four patients undergoing proton therapy with a fixed relative biological effectiveness (RBE) of 1.1 and a fraction dose of 1.8 Gy(RBE), new treatment plans were optimized with MCTP for both protons (with variable and fixed RBE) and helium ions (with variable RBE) under the same constraints derived from the initial clinical plans. The resulting dose distributions were dosimetrically compared in terms of dose volume histograms (DVH) parameters for the planning target volume (PTV) and the organs at risk (OARs), as well as dose difference maps. In most of the cases helium ion plans provided a similar PTV coverage as protons with a consistent trend of superior OAR sparing. The latter finding was attributed to the ability of helium ions to offer sharper distal and lateral dose fall-offs, as well as a more favorable differential RBE variation in target and normal tissue. Although more studies are needed to investigate the clinical potential of helium ions for different tumour entities, the results of this work based on an experimentally validated MC engine support the promise of this modality with state-of-the-art pencil beam scanning delivery, especially in case of tumours growing in close proximity of multiple OARs such as meningiomas.

SU-D-304-07: Application of Proton Boron Fusion Reaction to Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, J; Yoon, D; Shin, H

Purpose: we present the introduction of a therapy method using the proton boron fusion reaction. The purpose of this study is to verify the theoretical validity of proton boron fusion therapy using Monte Carlo simulations. Methods: After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton’s maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here we show thatmore » the effectiveness of the proton boron fusion therapy (PBFT) was verified using Monte Carlo simulations. Results: We found that a dramatic increase by more than half of the proton’s maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton’s maximum dose point was located within the boron uptake region (BUR). In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. Conclusion: This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.« less

Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

NASA Astrophysics Data System (ADS)

Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang, Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Yepes, Pablo; Woo, Shiao; Mohan, Radhe

2009-03-01

Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

Proton therapy detector studies under the experience gained at the CATANA facility

NASA Astrophysics Data System (ADS)

Cuttone, G.; Cirrone, G. A. P.; Di Rosa, F.; Lojacono, P. A.; Lo Nigro, S.; Marino, C.; Mongelli, V.; Patti, I. V.; Pittera, S.; Raffaele, L.; Russo, G.; Sabini, M. G.; Salamone, V.; Valastro, L. M.

2007-10-01

Proton therapy represents the most promising radiotherapy technique for external tumor treatments. At Laboratori Nazionali del Sud of the Istituto Nazionale di Fisica Nucleare (INFN-LNS), Catania (I), a proton therapy facility is active since March 2002 and 140 patients, mainly affected by choroidal and iris melanoma, have been successfully treated. Proton beams are characterized by higher dose gradients and linear energy transfer with respect to the conventional photon and electron beams, commonly used in medical centers for radiotherapy.In this paper, we report the experience gained in the characterization of different dosimetric systems, studied and/or developed during the last ten years in our proton therapy facility.

Proton beams in radiotherapy

NASA Astrophysics Data System (ADS)

Khoroshkov, V. S.; Minakova, E. I.

1998-11-01

A branch of radiology, proton therapy employs fast protons as a tool for the treatment of various, mainly oncological, diseases. The features of tissue ionization by protons (Bragg peak) facilitate a further step towards solving the principal challenge in radiology: to deliver a sufficiently high and homogeneous dose to virtually any tumour, while sparing healthy neighbouring tissues, organs and structures. The state of the art of proton therapy is described, as well as the main technical, physics and clinical results gained since the 1950s at high-energy physics centres worldwide. The future of proton therapy is connected with the construction of hospital-based facilities with dedicated medical accelerators and modern technical instrumentation.

Application of proton boron fusion reaction to radiation therapy: A Monte Carlo simulation study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Do-Kun; Jung, Joo-Young; Suh, Tae Suk, E-mail: suhsanta@catholic.ac.kr

2014-12-01

Three alpha particles are emitted from the point of reaction between a proton and boron. The alpha particles are effective in inducing the death of a tumor cell. After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton's maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here, we show that the effectiveness of the proton boron fusion therapymore » was verified using Monte Carlo simulations. We found that a dramatic increase by more than half of the proton's maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton's maximum dose point was located within the boron uptake region. In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.« less

The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widder, Joachim, E-mail: j.widder@umcg.nl; Schaaf, Arjen van der; Lambin, Philippe

Purpose: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Methods and Materials: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. Results: By analogy with biologically targeted therapies, the technology needs to be testedmore » in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Conclusions: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.« less

Simulation of prompt gamma-ray emission during proton radiotherapy.

PubMed

Verburg, Joost M; Shih, Helen A; Seco, Joao

2012-09-07

The measurement of prompt gamma rays emitted from proton-induced nuclear reactions has been proposed as a method to verify in vivo the range of a clinical proton radiotherapy beam. A good understanding of the prompt gamma-ray emission during proton therapy is key to develop a clinically feasible technique, as it can facilitate accurate simulations and uncertainty analysis of gamma detector designs. Also, the gamma production cross-sections may be incorporated as prior knowledge in the reconstruction of the proton range from the measurements. In this work, we performed simulations of proton-induced nuclear reactions with the main elements of human tissue, carbon-12, oxygen-16 and nitrogen-14, using the nuclear reaction models of the GEANT4 and MCNP6 Monte Carlo codes and the dedicated nuclear reaction codes TALYS and EMPIRE. For each code, we made an effort to optimize the input parameters and model selection. The results of the models were compared to available experimental data of discrete gamma line cross-sections. Overall, the dedicated nuclear reaction codes reproduced the experimental data more consistently, while the Monte Carlo codes showed larger discrepancies for a number of gamma lines. The model differences lead to a variation of the total gamma production near the end of the proton range by a factor of about 2. These results indicate a need for additional theoretical and experimental study of proton-induced gamma emission in human tissue.

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin

2015-01-01

Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727

Proton beam therapy in the management of skull base chordomas: systematic review of indications, outcomes, and implications for neurosurgeons.

PubMed

Matloob, Samir A; Nasir, Haleema A; Choi, David

2016-08-01

Chordomas are rare tumours affecting the skull base. There is currently no clear consensus on the post-surgical radiation treatments that should be used after maximal tumour resection. However, high-dose proton beam therapy is an accepted option for post-operative radiotherapy to maximise local control, and in the UK, National Health Service approval for funding abroad is granted for specific patient criteria. To review the indications and efficacy of proton beam therapy in the management of skull base chordomas. The primary outcome measure for review was the efficacy of proton beam therapy in the prevention of local occurrence. A systematic review of English and non-English articles using MEDLINE (1946-present) and EMBASE (1974-present) databases was performed. Additional studies were reviewed when referenced in other studies and not available on these databases. Search terms included chordoma or chordomas. The PRISMA guidelines were followed for reporting our findings as a systematic review. A total of 76 articles met the inclusion and exclusion criteria for this review. Limitations included the lack of documentation of the extent of primary surgery, tumour size, and lack of standardised outcome measures. Level IIb/III evidence suggests proton beam therapy given post operatively for skull base chordomas results in better survival with less damage to surrounding tissue. Proton beam therapy is a grade B/C recommended treatment modality for post-operative radiation therapy to skull base chordomas. In comparison to other treatment modalities long-term local control and survival is probably improved with proton beam therapy. Further, studies are required to directly compare proton beam therapy to other treatment modalities in selected patients.

Does Proton Therapy Offer Demonstrable Clinical Advantages for Treating Thoracic Tumors?

PubMed

Liao, Zhongxing; Gandhi, Saumil J; Lin, Steven H; Bradley, Jeffrey

2018-04-01

The finite range of proton beams in tissues offers unique dosimetric advantages that theoretically allow dose to the target to be escalated while minimizing exposure of surrounding tissues and thus minimizing radiation-induced toxicity. This theoretical advantage has led to widespread adoption of proton therapy around the world for a wide variety of tumors at different anatomical sites. Many treatment-planning comparisons have shown that proton therapy has substantial dosimetric advantages over conventional radiotherapy. However, given the significant difference in cost for proton vs conventional photon therapy, thorough investigation of the evidence of proton therapy's clinical benefits in terms of toxicity and survival is warranted. Some data from retrospective studies, single-arm prospective studies, and a very few randomized clinical trials comparing these modalities are beginning to emerge. In this review, we examine the available data with regard to proton therapy for thoracic malignancies. We begin by discussing the unique challenges involved in treating moving targets with significant tissue heterogeneity and the technologic efforts underway to overcome these challenges. We then discuss the rationale for minimizing normal tissue toxicity, particularly pulmonary, cardiac, and hematologic toxicity, within the context of previously unsuccessful attempts at dose escalation for lung and esophageal cancer. Finally, we explore strategies for accelerating the development of trials aimed at measuring meaningful clinical endpoints and for maximizing the value of proton therapy by personalizing its use for individual patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Proton therapy to the subdiaphragmatic region in the management of patients with Hodgkin lymphoma.

PubMed

Sachsman, Suzanne; Hoppe, Bradford S; Mendenhall, Nancy P; Holtzman, Adam; Li, Zuofeng; Slayton, William; Joyce, Mike; Sandler, Eric; Flampouri, Stella

2015-07-01

Twelve consecutive patients with classical Hodgkin lymphoma (HL) involving diaphragmatic or subdiaphragmatic regions were treated on an institutional review board-approved outcomes tracking protocol. All patients underwent treatment with proton therapy following chemotherapy and had comparative three-dimensional conformal photon radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans to evaluate differences in dose to organs at risk (OARs). Among the cohort, stomach doses with 3DCRT, IMRT and proton therapy were 21 Gy (median), 14 Gy and 6 Gy, respectively. Median dose reductions with proton therapy compared with 3DCRT and IMRT were 13 Gy (p = 0.0022) and 8 Gy (p = 0.0022) for the stomach. Additionally, there was significant dose reduction using proton therapy for the liver, pancreas, bowel, left kidney and right kidney. Proton therapy reduces the dose to the stomach, liver, pancreas, small bowel and kidneys compared with 3DCRT or IMRT in patients with HL requiring abdominal radiotherapy. These dose reductions are expected to translate into lower risks of secondary cancers and other late toxicities in survivors of HL.

SU-F-T-194: Analyzing the Effect of Range Shifter Air Gap On TPS Dose Modeling Accuracy in Superficial PBS Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirey, R; Wu, H

2016-06-15

Purpose: Treatment planning systems (TPS) may not accurately model superficial dose distributions of range shifted proton pencil beam scanning (PBS) treatments. Numerous patient-specific QA tests performed on superficially treated PBS plans have shown a consistent overestimate of dose by the TPS. This study quantifies variations between TPS planned dose and measured dose as a function of range shifter air gap and treatment depths up to 5 cm. Methods: PBS treatment plans were created in the TPS to uniformly irradiate a volume of solid water. One plan was created for each range shifter position analyzed, and all plans utilized identical dosemore » optimization parameters. Each optimized plan was analyzed in the TPS to determine the planned dose at varying depths. A PBS proton therapy system with a 3.5 cm lucite range shifter delivered the treatment plans, and a parallel plate chamber embedded in RW3 solid water measured dose at shallow depths for each air gap. Differences between measured and planned doses were plotted and analyzed. Results: The data show that the TPS more accurately models superficial dose as the air gap between the range shifter and patient surface decreases. Air gaps less than 10 cm have an average dose difference of only 1.6%, whereas air gaps between 10 and 20 cm differ by 3.0% and gaps greater than 20 cm differ by 4.4%. Conclusion: This study has shown that the TPS is unable to accurately model superficial dose with a large range shifter air gap. Dose differences greater than 3% will likely cause QA failure, as many institutions analyze patient QA with a 3%/3mm gamma analysis. For superficial PBS therapy, range shifter positions should be chosen to keep the air gap less then 10 cm when patient setup and gantry geometry allow.« less

Proton radiography and tomography with application to proton therapy

PubMed Central

Allinson, N M; Evans, P M

2015-01-01

Proton radiography and tomography have long promised benefit for proton therapy. Their first suggestion was in the early 1960s and the first published proton radiographs and CT images appeared in the late 1960s and 1970s, respectively. More than just providing anatomical images, proton transmission imaging provides the potential for the more accurate estimation of stopping-power ratio inside a patient and hence improved treatment planning and verification. With the recent explosion in growth of clinical proton therapy facilities, the time is perhaps ripe for the imaging modality to come to the fore. Yet many technical challenges remain to be solved before proton CT scanners become commonplace in the clinic. Research and development in this field is currently more active than at any time with several prototype designs emerging. This review introduces the principles of proton radiography and tomography, their historical developments, the raft of modern prototype systems and the primary design issues. PMID:26043157

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boehling, Nicholas S.; Grosshans, David R., E-mail: dgrossha@mdanderson.org; Bluett, Jaques B.

Purpose: Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials: IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV)more » coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms. Results: The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%{sup Asterisk-Operator }), dentate gyrus (27.3, 75.0%{sup Asterisk-Operator }), and subventricular zone (4.5, 57.8%{sup Asterisk-Operator }). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3{sup Asterisk-Operator }, 100.0%{sup Asterisk-Operator }; middle cerebral arteries, 25.9%{sup Asterisk-Operator }, 100%{sup Asterisk-Operator }; anterior communicating arteries, 30.8{sup Asterisk-Operator }, 41.7%{sup Asterisk-Operator }; and carotid arteries, 51.5{sup Asterisk-Operator }, 77.6{sup Asterisk-Operator }). Relative reduction of integral dose to the infratentorial brain (190.7{sup Asterisk-Operator }, 109.7%{sup Asterisk-Operator }), supratentorial brain without PTV (9.6, 26.8%{sup Asterisk-Operator }), brainstem (45.6, 22.4%{sup Asterisk-Operator }), and whole brain without PTV (19.4{sup Asterisk-Operator }, 34.4%{sup Asterisk-Operator }) were recorded with the use of proton therapy. ({sup Asterisk-Operator }Differences were significant based on Friedman's test with Bonferroni-Dunn correction, {alpha} = 0.05) Conclusions: The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.« less

Comparison of proton therapy treatment planning for head tumors with a pencil beam algorithm on dual and single energy CT images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hudobivnik, Nace; Dedes, George; Parodi, Katia

2016-01-15

Purpose: Dual energy CT (DECT) has recently been proposed as an improvement over single energy CT (SECT) for stopping power ratio (SPR) estimation for proton therapy treatment planning (TP), thereby potentially reducing range uncertainties. Published literature investigated phantoms. This study aims at performing proton therapy TP on SECT and DECT head images of the same patients and at evaluating whether the reported improved DECT SPR accuracy translates into clinically relevant range shifts in clinical head treatment scenarios. Methods: Two phantoms were scanned at a last generation dual source DECT scanner at 90 and 150 kVp with Sn filtration. The firstmore » phantom (Gammex phantom) was used to calibrate the scanner in terms of SPR while the second served as evaluation (CIRS phantom). DECT images of five head trauma patients were used as surrogate cancer patient images for TP of proton therapy. Pencil beam algorithm based TP was performed on SECT and DECT images and the dose distributions corresponding to the optimized proton plans were calculated using a Monte Carlo (MC) simulation platform using the same patient geometry for both plans obtained from conversion of the 150 kVp images. Range shifts between the MC dose distributions from SECT and DECT plans were assessed using 2D range maps. Results: SPR root mean square errors (RMSEs) for the inserts of the Gammex phantom were 1.9%, 1.8%, and 1.2% for SECT phantom calibration (SECT{sub phantom}), SECT stoichiometric calibration (SECT{sub stoichiometric}), and DECT calibration, respectively. For the CIRS phantom, these were 3.6%, 1.6%, and 1.0%. When investigating patient anatomy, group median range differences of up to −1.4% were observed for head cases when comparing SECT{sub stoichiometric} with DECT. For this calibration the 25th and 75th percentiles varied from −2% to 0% across the five patients. The group median was found to be limited to 0.5% when using SECT{sub phantom} and the 25th and 75th percentiles varied from −1% to 2%. Conclusions: Proton therapy TP using a pencil beam algorithm and DECT images was performed for the first time. Given that the DECT accuracy as evaluated by two phantoms was 1.2% and 1.0% RMSE, it is questionable whether the range differences reported here are significant.« less

Review of 3D image data calibration for heterogeneity correction in proton therapy treatment planning.

PubMed

Zhu, Jiahua; Penfold, Scott N

2016-06-01

Correct modelling of the interaction parameters of patient tissues is of vital importance in proton therapy treatment planning because of the large dose gradients associated with the Bragg peak. Different 3D imaging techniques yield different information regarding these interaction parameters. Given the rapidly expanding interest in proton therapy, this review is written to make readers aware of the current challenges in accounting for tissue heterogeneities and the imaging systems that are proposed to tackle these challenges. A summary of the interaction parameters of interest in proton therapy and the current and developmental 3D imaging techniques used in proton therapy treatment planning is given. The different methods to translate the imaging data to the interaction parameters of interest are reviewed and a summary of the implementations in several commercial treatment planning systems is presented.

Comparison of organ-at-risk sparing and plan robustness for spot-scanning proton therapy and volumetric modulated arc photon therapy in head-and-neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barten, Danique L. J., E-mail: d.barten@vumc.nl; Tol, Jim P.; Dahele, Max

Purpose: Proton radiotherapy for head-and-neck cancer (HNC) aims to improve organ-at-risk (OAR) sparing over photon radiotherapy. However, it may be less robust for setup and range uncertainties. The authors investigated OAR sparing and plan robustness for spot-scanning proton planning techniques and compared these with volumetric modulated arc therapy (VMAT) photon plans. Methods: Ten HNC patients were replanned using two arc VMAT (RapidArc) and spot-scanning proton techniques. OARs to be spared included the contra- and ipsilateral parotid and submandibular glands and individual swallowing muscles. Proton plans were made using Multifield Optimization (MFO, using three, five, and seven fields) and Single-field Optimizationmore » (SFO, using three fields). OAR sparing was evaluated using mean dose to composite salivary glands (Comp{sub Sal}) and composite swallowing muscles (Comp{sub Swal}). Plan robustness was determined for setup and range uncertainties (±3 mm for setup, ±3% HU) evaluating V95% and V107% for clinical target volumes. Results: Averaged over all patients Comp{sub Sal}/Comp{sub Swal} mean doses were lower for the three-field MFO plans (14.6/16.4 Gy) compared to the three-field SFO plans (20.0/23.7 Gy) and VMAT plans (23.0/25.3 Gy). Using more than three fields resulted in differences in OAR sparing of less than 1.5 Gy between plans. SFO plans were significantly more robust than MFO plans. VMAT plans were the most robust. Conclusions: MFO plans had improved OAR sparing but were less robust than SFO and VMAT plans, while SFO plans were more robust than MFO plans but resulted in less OAR sparing. Robustness of the MFO plans did not increase with more fields.« less

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

PubMed

Hirano, Emi; Fuji, Hiroshi; Onoe, Tsuyoshi; Kumar, Vinay; Shirato, Hiroki; Kawabuchi, Koichi

2014-03-01

The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient

NASA Astrophysics Data System (ADS)

Zhang, Rui; Howell, Rebecca M.; Giebeler, Annelise; Taddei, Phillip J.; Mahajan, Anita; Newhauser, Wayne D.

2013-02-01

Pediatric patients who received radiation therapy are at risk of developing side effects such as radiogenic second cancer. We compared proton and photon therapies in terms of the predicted risk of second cancers for a 4 year old medulloblastoma patient receiving craniospinal irradiation (CSI). Two CSI treatment plans with 23.4 Gy or Gy (RBE) prescribed dose were computed: a three-field 6 MV photon therapy plan and a four-field proton therapy plan. The primary doses for both plans were determined using a commercial treatment planning system. Stray radiation doses for proton therapy were determined from Monte Carlo simulations, and stray radiation doses for photon therapy were determined from measured data. Dose-risk models based on the Biological Effects of Ionization Radiation VII report were used to estimate the risk of second cancer in eight tissues/organs. Baseline predictions of the relative risk for each organ were always less for proton CSI than for photon CSI at all attained ages. The total lifetime attributable risk of the incidence of second cancer considered after proton CSI was much lower than that after photon CSI, and the ratio of lifetime risk was 0.18. Uncertainty analysis revealed that the qualitative findings of this study were insensitive to any plausible changes of dose-risk models and mean radiation weighting factor for neutrons. Proton therapy confers lower predicted risk of second cancer than photon therapy for the pediatric medulloblastoma patient.

The Current Status and Future Directions of Heavy Charged Particle Therapy in Medicine

NASA Astrophysics Data System (ADS)

Levy, Richard P.; Blakely, Eleanor A.; Chu, William T.; Coutrakon, George B.; Hug, Eugen B.; Kraft, Gerhard; Tsujii, Hirohiko

2009-03-01

As aggressive, 3D-conformal treatment has become the clearly accepted goal of radiation oncology, heavy charged-particle treatment with protons and heavier ions has concurrently and relentlessly ascended to the forefront. Protons and helium nuclei, with relatively low linear-energy-transfer (LET) properties, have consistently been demonstrated to be beneficial for aggressive (high-dose) local treatment of many types of tumors. Protons have been applied to the majority of solid tumors, and have reached a high degree of general acceptance in radiation oncology after three decades and 55,000 patients treated. However, some 15% to 20% of tumor types have proven resistant to even the most aggressive low-LET irradiation. For these radio-resistant tumors, treatment with heavier ions (e.g., carbon) offers great potential benefit. These high-LET particles have increased relative biological effectiveness (RBE) that reaches its maximum in the Bragg peak. Irradiation with these heavier ions offers the unique combination of excellent 3D-dose distribution and increased RBE. We are presently witnessing several, important parallel developments in particle therapy. Protons will likely continue their exponential growth phase, and more compact design systems will make protons available to a larger patient population—thus becoming the "heavy charged particle of choice" for Cancer Centers with limited financial resources. In parallel, major academic efforts will further advance the field of heavier ion therapy, exploring all opportunities for particle treatment and continuing the search for the ideal particle(s) for specific tumors. The future of ion therapy will be best realized by clinical trials that have ready access to top-quality delivery of both protons and heavier ions that can be accurately shaped for treatment of a specific pathology, and which will permit direct randomized-trial comparison of the effectiveness of the various ions for different diseases. Optimal results will require: (1) sophisticated target delineation that integrates CT, MRI and PET imaging; (2) reliable RBE modeling algorithms; (3) efficient beam-scanning technology that compensates for organ movements; (4) online beam control proximal to and within the patient; and (5) better understanding of dose-fractionation parameters. The current status and the anticipated future directions of the role of particle therapy in medicine is a complex subject that involves a very intimate interplay of radiobiology, accelerator physics and radiation oncology. The intention of this relatively brief manuscript is to describe the underlying principles, present the historical developments, highlight the clinical results, focus on the technical advances, and suggest likely future directions. We have also attempted to present a balanced, consensus view of the past achievements and current strategies in particle therapy, in a manner of interest both to long-term experts and to educated newcomers to this field.

Optical dosimetry of radiotherapy beams using Cherenkov radiation: the relationship between light emission and dose.

PubMed

Glaser, Adam K; Zhang, Rongxiao; Gladstone, David J; Pogue, Brian W

2014-07-21

Recent studies have proposed that light emitted by the Cherenkov effect may be used for a number of radiation therapy dosimetry applications. There is a correlation between the captured light and expected dose under certain conditions, yet discrepancies have also been observed and a complete examination of the theoretical differences has not been done. In this study, a fundamental comparison between the Cherenkov emission and absorbed dose was explored for x-ray photons, electrons, and protons using both a theoretical and Monte Carlo-based analysis. Based on the findings of where dose correlates with Cherenkov emission, it was concluded that for x-ray photons the light emission would be optimally suited for narrow beam stereotactic radiation therapy and surgery validation studies, for verification of dynamic intensity-modulated and volumetric modulated arc therapy treatment plans in water tanks, near monoenergetic sources (e.g., Co-60 and brachy therapy sources) and also for entrance and exit surface imaging dosimetry of both narrow and broad beams. For electron use, Cherenkov emission was found to be only suitable for surface dosimetry applications. Finally, for proton dosimetry, there exists a fundamental lack of Cherenkov emission at the Bragg peak, making the technique of little use, although post-irradiation detection of light emission from radioisotopes could prove to be useful.

Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected].

PubMed

Heidelbaugh, Joel J; Goldberg, Kathleen L; Inadomi, John M

2009-03-01

Proton pump inhibitors (PPIs) are superior to histamine-2 receptor antagonists for the treatment of gastroesophageal reflux disease (GERD) and erosive esophagitis. Antisecretory therapy (AST), however, accounts for significant cost expenditure in the United States including over-the-counter and prescription formulations. Moreover, emerging data illustrate the potential risks associated with long-term PPI therapy including variations in bioavailability of common medications, vitamin B12 deficiency, Clostridium difficile-associated diarrhea, community-acquired pneumonia, and hip fracture. For these reasons, it is imperative to use the lowest dose of drug necessary to achieve desired therapeutic goals. This may entail the use of step-down, step-off, or on-demand PPI therapy for the treatment of GERD. In addition, PPIs are the most commonly used medications for stress ulcer prophylaxis (SUP), despite little evidence to support their use. Compounding this problem is evidence that patients erroneously administered SUP are often discharged on long-term PPI therapy. Pharmacy-driven step-down orders, limitation of the use of PPIs for SUP in non-ICU settings, and meticulous chart review to ensure that hospitalized patients are not discharged home on a PPI without an appropriate indication are interventions that can ensure proper PPI utilization with minimal of risk and optimization of cost-effectiveness.

New Strategies in Radiation Therapy: Exploiting the Full Potential of Protons

PubMed Central

Mohan, Radhe; Mahajan, Anita; Minsky, Bruce D.

2013-01-01

Protons provide significant dosimetric advantages compared with photons due to their unique depth-dose distribution characteristics. However, they are more sensitive to the effects of intra- and inter-treatment fraction anatomic variations and uncertainties in treatment setup. Furthermore, in the current practice of proton therapy, the biological effectiveness of protons relative to photons is assumed to have a generic fixed value of 1.1. However, this is a simplification, and it is likely higher in different portions of the proton beam. Current clinical practice and trials have not fully exploited the unique physical and biological properties of protons. Intensity-modulated proton therapy, with its ability to manipulate energies (in addition to intensities), provides an entirely new dimension, which, with ongoing research, has considerable potential to increase the therapeutic ratio. PMID:24077353

New strategies in radiation therapy: exploiting the full potential of protons.

PubMed

Mohan, Radhe; Mahajan, Anita; Minsky, Bruce D

2013-12-01

Protons provide significant dosimetric advantages compared with photons because of their unique depth-dose distribution characteristics. However, they are more sensitive to the effects of intra- and intertreatment fraction anatomic variations and uncertainties in treatment setup. Furthermore, in the current practice of proton therapy, the biologic effectiveness of protons relative to photons is assumed to have a generic fixed value of 1.1. However, this is a simplification, and it is likely higher in different portions of the proton beam. Current clinical practice and trials have not fully exploited the unique physical and biologic properties of protons. Intensity-modulated proton therapy, with its ability to manipulate energies (in addition to intensities), provides an entirely new dimension, which, with ongoing research, has considerable potential to increase the therapeutic ratio. ©2013 AACR.

SU-E-T-254: Optimization of GATE and PHITS Monte Carlo Code Parameters for Uniform Scanning Proton Beam Based On Simulation with FLUKA General-Purpose Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurosu, K; Department of Medical Physics ' Engineering, Osaka University Graduate School of Medicine, Osaka; Takashina, M

Purpose: Monte Carlo codes are becoming important tools for proton beam dosimetry. However, the relationships between the customizing parameters and percentage depth dose (PDD) of GATE and PHITS codes have not been reported which are studied for PDD and proton range compared to the FLUKA code and the experimental data. Methods: The beam delivery system of the Indiana University Health Proton Therapy Center was modeled for the uniform scanning beam in FLUKA and transferred identically into GATE and PHITS. This computational model was built from the blue print and validated with the commissioning data. Three parameters evaluated are the maximummore » step size, cut off energy and physical and transport model. The dependence of the PDDs on the customizing parameters was compared with the published results of previous studies. Results: The optimal parameters for the simulation of the whole beam delivery system were defined by referring to the calculation results obtained with each parameter. Although the PDDs from FLUKA and the experimental data show a good agreement, those of GATE and PHITS obtained with our optimal parameters show a minor discrepancy. The measured proton range R90 was 269.37 mm, compared to the calculated range of 269.63 mm, 268.96 mm, and 270.85 mm with FLUKA, GATE and PHITS, respectively. Conclusion: We evaluated the dependence of the results for PDDs obtained with GATE and PHITS Monte Carlo generalpurpose codes on the customizing parameters by using the whole computational model of the treatment nozzle. The optimal parameters for the simulation were then defined by referring to the calculation results. The physical model, particle transport mechanics and the different geometrybased descriptions need accurate customization in three simulation codes to agree with experimental data for artifact-free Monte Carlo simulation. This study was supported by Grants-in Aid for Cancer Research (H22-3rd Term Cancer Control-General-043) from the Ministry of Health, Labor and Welfare of Japan, Grants-in-Aid for Scientific Research (No. 23791419), and JSPS Core-to-Core program (No. 23003). The authors have no conflict of interest.« less

Clinical results of proton beam therapy for twenty older patients with esophageal cancer

PubMed Central

Ono, Takashi; Nakamura, Tatsuya; Azami, Yusuke; Yamaguchi, Hisashi; Hayashi, Yuichiro; Suzuki, Motohisa; Hatayama, Yoshiomi; Tsukiyama, Iwao; Hareyama, Masato; Kikuchi, Yasuhiro; Nemoto, Kenji

2015-01-01

Background In an aging society, increasing number of older patients are diagnosed with esophageal cancer. The purpose of this study was to assess the clinical efficacy and safety of proton beam therapy for older patients with esophageal cancer. Patients and methods. Older patients (age: ≥ 65 years) newly diagnosed with esophageal cancer between January 2009 and June 2013 were enrolled in this study. All patients underwent either proton beam therapy alone or proton beam therapy with initial X-ray irradiation. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results Twenty patients were eligible for this study and all completed the treatment. The median age was 78 years (range: 65–89 years) and the median follow-up time was 26.5 months (range: 6–62 months). Seven patients had lymph node metastases and 10 had stage II/III cancer. The median dose of proton beam therapy was 72.6 Gy relative biological dose effectiveness (RBE) (range: 66–74.8 Gy [RBE]) for proton beam therapy alone and 33 Gy (RBE) (range: 30.8–39.6 Gy [RBE]; total dose range: 66.8–75.6 Gy [RBE]) for proton beam therapy with initial X-ray irradiation. The 2-year overall survival rate was 81.8% (95% confidence interval [CI]: 62.4%–100%), and the 2-year local control rate was 89.4% (95% CI: 75.5%–100%). Grade 2 or 3 toxicities occurred in some cases; however, no grade 4 or 5 toxicity was observed. Conclusions High-dose (66–75.6 Gy [RBE]) proton beam therapy without chemotherapy was an efficacious and safe treatment for older patients with esophageal cancer. PMID:26834524

Development of a remote proton radiation therapy solution over internet2.

PubMed

Belard, Arnaud; Tinnel, Brent; Wilson, Steve; Ferro, Ralph; O'Connell, John

2009-12-01

Through our existing partnership, our research program has leveraged the benefits of proton radiation therapy through the development a robust telemedicine solution for remote proton therapy planning. Our proof-of-concept system provides a cost-effective and functional videoconferencing desktop platform for both ad-hoc and scheduled communication, as well as a robust interface for data collaboration (application-sharing of a commercial radiation treatment planning package). Over a 2-year period, our evaluation of this model has highlighted the inherent benefits of this affordable remote treatment planning solution, i.e., (1) giving physicians the ability to remotely participate in refining and generating proton therapy plans via a secure and robust Internet2 VPN tunnel to the University of Pennsylvania's commercial proton treatment planning package; (2) allowing cancer-care providers sending patients to a proton treatment facility to participate in treatment planning decisions by enabling referring or accepting providers to initiate ad-hoc, point-to-point communication with their counterparts to clarify and resolve issues arising before or during patient treatment; and thus (3) allowing stewards of an otherwise highly centralized resource the ability to encourage wider participation with and referrals to sparsely located proton treatment centers by adapting telemedicine techniques that allow sharing of proton therapy planning services. We believe that our elegant and very affordable approach to remote proton treatment planning opens the door to greater worldwide referrals to the scarce resource of proton treatment units and wide-ranging scientific collaboration, both nationally and internationally.

Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uh, Jinsoo, E-mail: jinsoo.uh@stjude.org; Merchant, Thomas E.; Li, Yimei

Purpose: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. Methods and Materials: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51more » atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. Results: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non–surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. Conclusions: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect.« less

Comparing gold nano-particle enhanced radiotherapy with protons, megavoltage photons and kilovoltage photons: a Monte Carlo simulation.

PubMed

Lin, Yuting; McMahon, Stephen J; Scarpelli, Matthew; Paganetti, Harald; Schuemann, Jan

2014-12-21

Gold nanoparticles (GNPs) have shown potential to be used as a radiosensitizer for radiation therapy. Despite extensive research activity to study GNP radiosensitization using photon beams, only a few studies have been carried out using proton beams. In this work Monte Carlo simulations were used to assess the dose enhancement of GNPs for proton therapy. The enhancement effect was compared between a clinical proton spectrum, a clinical 6 MV photon spectrum, and a kilovoltage photon source similar to those used in many radiobiology lab settings. We showed that the mechanism by which GNPs can lead to dose enhancements in radiation therapy differs when comparing photon and proton radiation. The GNP dose enhancement using protons can be up to 14 and is independent of proton energy, while the dose enhancement is highly dependent on the photon energy used. For the same amount of energy absorbed in the GNP, interactions with protons, kVp photons and MV photons produce similar doses within several nanometers of the GNP surface, and differences are below 15% for the first 10 nm. However, secondary electrons produced by kilovoltage photons have the longest range in water as compared to protons and MV photons, e.g. they cause a dose enhancement 20 times higher than the one caused by protons 10 μm away from the GNP surface. We conclude that GNPs have the potential to enhance radiation therapy depending on the type of radiation source. Proton therapy can be enhanced significantly only if the GNPs are in close proximity to the biological target.

Development of a Multileaf Collimator for Proton Radiotherapy

DTIC Science & Technology

2011-06-01

to treat shallow depths was also simulated and commissioned in Eclipse . In order to calibrate the number of simulated protons per MU, a reference ...beam technology for proton radiotherapy, and the fourth year of the project to develop image guided treatment protocols for proton therapy. This...radiotherapy to proton therapy, and to develop a decision-making algorithm to maximize the efficiency of the facility. This report describes the

Design study of an in situ PET scanner for use in proton beam therapy

NASA Astrophysics Data System (ADS)

Surti, S.; Zou, W.; Daube-Witherspoon, M. E.; McDonough, J.; Karp, J. S.

2011-05-01

Proton beam therapy can deliver a high radiation dose to a tumor without significant damage to surrounding healthy tissue or organs. One way of verifying the delivered dose distribution is to image the short-lived positron emitters produced by the proton beam as it travels through the patient. A potential solution to the limitations of PET imaging in proton beam therapy is the development of a high sensitivity, in situ PET scanner that starts PET imaging almost immediately after patient irradiation while the patient is still lying on the treatment bed. A partial ring PET design is needed for this application in order to avoid interference between the PET detectors and the proton beam, as well as restrictions on patient positioning on the couch. A partial ring also allows us to optimize the detector separation (and hence the sensitivity) for different patient sizes. Our goal in this investigation is to evaluate an in situ PET scanner design for use in proton therapy that provides tomographic imaging in a partial ring scanner design using time-of-flight (TOF) information and an iterative reconstruction algorithm. GEANT4 simulation of an incident proton beam was used to produce a positron emitter distribution, which was parameterized and then used as the source distribution inside a water-filled cylinder for EGS4 simulations of a PET system. Design optimization studies were performed as a function of crystal type and size, system timing resolution, scanner angular coverage and number of positron emitter decays. Data analysis was performed to measure the accuracy of the reconstructed positron emitter distribution as well as the range of the positron emitter distribution. We simulated scanners with varying crystal sizes (2-4 mm) and type (LYSO and LaBr3) and our results indicate that 4 mm wide LYSO or LaBr3 crystals (resulting in 4-5 mm spatial resolution) are adequate; for a full-ring, non-TOF scanner we predict a low bias (<0.6 mm) and a good precision (<1 mm) in the estimated range relative to the simulated positron distribution. We then varied the angular acceptance of the scanner ranging from 1/2 to 2/3 of 2π a partial ring TOF imaging with good timing resolution (<=600 ps) is necessary to produce accurate tomographic images. A two-third ring scanner with 300 ps timing resolution leads to a bias of 1.0 mm and a precision of 1.4 mm in the range estimate. With a timing resolution of 600 ps, the bias increases to 2.0 mm while the precision in the range estimate is similar. For a half-ring scanner design, more distortions are present in the image, which is characterized by the increased error in the profile difference estimate. We varied the number of positron decays imaged by the PET scanner by an order of magnitude and we observe some decrease in the precision of the range estimate for lower number of decays, but all partial ring scanner designs studied have a precision <=1.5 mm. The largest number tested, 150 M total positron decays, is considered realistic for a clinical fraction of delivered dose, while the range of positron decays investigated in this work covers a variable number of situations corresponding to delays in scan start time and the total scan time. Thus, we conclude that for partial ring systems, an angular acceptance of at least 1/2 (of 2π) together with timing resolution of 300 ps is needed to achieve accurate and precise range estimates. With 600 ps timing resolution an angular acceptance of 2/3 (of 2π) is required to achieve satisfactory range estimates. These results indicate that it would be feasible to develop a partial-ring dedicated PET scanner based on either LaBr3 or LYSO to accurately characterize the proton dose for therapy planning.

Monte Carlo simulation of secondary neutron dose for scanning proton therapy using FLUKA

PubMed Central

Lee, Chaeyeong; Lee, Sangmin; Lee, Seung-Jae; Song, Hankyeol; Kim, Dae-Hyun; Cho, Sungkoo; Jo, Kwanghyun; Han, Youngyih; Chung, Yong Hyun

2017-01-01

Proton therapy is a rapidly progressing field for cancer treatment. Globally, many proton therapy facilities are being commissioned or under construction. Secondary neutrons are an important issue during the commissioning process of a proton therapy facility. The purpose of this study is to model and validate scanning nozzles of proton therapy at Samsung Medical Center (SMC) by Monte Carlo simulation for beam commissioning. After the commissioning, a secondary neutron ambient dose from proton scanning nozzle (Gantry 1) was simulated and measured. This simulation was performed to evaluate beam properties such as percent depth dose curve, Bragg peak, and distal fall-off, so that they could be verified with measured data. Using the validated beam nozzle, the secondary neutron ambient dose was simulated and then compared with the measured ambient dose from Gantry 1. We calculated secondary neutron dose at several different points. We demonstrated the validity modeling a proton scanning nozzle system to evaluate various parameters using FLUKA. The measured secondary neutron ambient dose showed a similar tendency with the simulation result. This work will increase the knowledge necessary for the development of radiation safety technology in medical particle accelerators. PMID:29045491

Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma.

PubMed

Jacola, Lisa M; Conklin, Heather M; Scoggins, Matthew A; Ashford, Jason M; Merchant, Thomas E; Mandrell, Belinda N; Ogg, Robert J; Curtis, Elizabeth; Wise, Merrill S; Indelicato, Daniel J; Crabtree, Valerie M

2016-07-01

Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy. Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy. EDS was identified in 76% of the patients and was significantly related to increased HI extent (p = .04). There was no relationship between CPT performance during fMRI and HI or EDS. Visual examination of group composite fMRI images revealed greater spatial extent of activation in frontal cortical regions in patients with EDS, consistent with a compensatory activation hypothesis. Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pencil beam scanning proton therapy vs rotational arc radiation therapy: A treatment planning comparison for postoperative oropharyngeal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Apinorasethkul, Ontida, E-mail: Ontida.a@gmail.com; Kirk, Maura; Teo, Kevin

Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals.more » Mean doses were significantly lower in the proton plans for the oral cavity (1771 cGy photon vs 293 cGy proton, p < 0.001), contralateral parotid (1796 cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608 cGy photon vs 3251 cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.« less

Monte Carlo simulations of a low energy proton beamline for radiobiological experiments.

PubMed

Dahle, Tordis J; Rykkelid, Anne Marit; Stokkevåg, Camilla H; Mairani, Andrea; Görgen, Andreas; Edin, Nina J; Rørvik, Eivind; Fjæra, Lars Fredrik; Malinen, Eirik; Ytre-Hauge, Kristian S

2017-06-01

In order to determine the relative biological effectiveness (RBE) of protons with high accuracy, radiobiological experiments with detailed knowledge of the linear energy transfer (LET) are needed. Cell survival data from high LET protons are sparse and experiments with low energy protons to achieve high LET values are therefore required. The aim of this study was to quantify LET distributions from a low energy proton beam by using Monte Carlo (MC) simulations, and to further compare to a proton beam representing a typical minimum energy available at clinical facilities. A Markus ionization chamber and Gafchromic films were employed in dose measurements in the proton beam at Oslo Cyclotron Laboratory. Dose profiles were also calculated using the FLUKA MC code, with the MC beam parameters optimized based on comparisons with the measurements. LET spectra and dose-averaged LET (LET d ) were then estimated in FLUKA, and compared with LET calculated from an 80 MeV proton beam. The initial proton energy was determined to be 15.5 MeV, with a Gaussian energy distribution of 0.2% full width at half maximum (FWHM) and a Gaussian lateral spread of 2 mm FWHM. The LET d increased with depth, from approximately 5 keV/μm in the entrance to approximately 40 keV/μm in the distal dose fall-off. The LET d values were considerably higher and the LET spectra were much narrower than the corresponding spectra from the 80 MeV beam. MC simulations accurately modeled the dose distribution from the proton beam and could be used to estimate the LET at any position in the setup. The setup can be used to study the RBE for protons at high LET d , which is not achievable in clinical proton therapy facilities.

TU-G-BRCD-01: Will the High Cost of Proton Therapy Facilities Limit the Availability of Proton Therapy Treatment?

PubMed

Maughan, R

2012-06-01

The potential dose distribution advantages associated with proton therapy, and particularly with pencil beam scanning (PBS) techniques, have lead to considerable interest in this modality in recent years. However, the large capital expenditure necessary for such a project requires careful financial consideration and business planning. The complexity of the beam delivery systems impacts the capital expenditure and the PBS only systems presently being advocated can reduce these costs. Also several manufacturers are considering "one-room" facilities as less expensive alternatives to multi-room facilities. This presentation includes a brief introduction to beam delivery options (passive scattering, uniform and modulated scanning) and some of the new technologies proposed for providing less expensive proton therapy systems. Based on current experience, data on proton therapy center start-up costs, running costs and the financial challenges associated with making this highly conformal therapy more widely available will be discussed. Issues associated with proton therapy implementation that are key to project success include strong project management, vendor cooperation and collaboration, staff recruitment and training. Time management during facility start up is a major concern, particularly in multi-room systems, where time must be shared between continuing vendor system validation, verification and acceptance testing, and user commissioning and patient treatments. The challenges associated with facility operation during this period and beyond are discussed, focusing on how standardization of process, downtime and smart scheduling can influence operational efficiency. 1. To understand the available choices for proton therapy facilities, the different beam delivery systems and the financial implications associated with these choices. 2. To understand the key elements necessary for successfully implementing a proton therapy program. 3. To understand the challenges associated with on-going facility management to achieve an efficient fully operational system. © 2012 American Association of Physicists in Medicine.

Predicted Rate of Secondary Malignancies Following Adjuvant Proton Versus Photon Radiation Therapy for Thymoma.

PubMed

Vogel, J; Lin, L; Litzky, L A; Berman, A T; Simone, C B

2017-10-01

Thymic malignancies are the most common tumors of the anterior mediastinum. The benefit of adjuvant radiation therapy for stage II disease remains controversial, and patients treated with adjuvant radiation therapy are at risk of late complications, including radiation-induced secondary malignant neoplasms (SMNs), that may reduce the overall benefit of treatment. We assess the risk of predicted SMNs following adjuvant proton radiation therapy compared with photon radiation therapy after resection of stage II thymic malignancies to determine whether proton therapy improves the risk-benefit ratio. Ten consecutive patients treated with double-scattered proton beam radiation therapy (DS-PBT) were prospectively enrolled in an institutional review board-approved proton registry study. All patients were treated with DS-PBT. Intensity modulated radiation therapy (IMRT) plans for comparison were generated. SMN risk was calculated based on organ equivalent dose. Patients had a median age of 65 years (range, 25-77 years), and 60% were men. All patients had stage II disease, and many had close or positive margins (60%). The median dose was 50.4 Gy (range, 50.4-54.0 Gy) in 1.8-Gy relative biological effectiveness daily fractions. No differences in target coverage were seen with DS-PBT compared with IMRT plans. Significant reductions were seen in mean and volumetric lung, heart, and esophageal doses with DS-PBT compared with IMRT plans (all P≤.01). Significant reductions in SMNs in the lung, breast, esophagus, skin, and stomach were seen with DS-PBT compared with IMRT. For patients with thymoma diagnosed at the median national age, 5 excess secondary malignancies per 100 patients would be avoided by treating them with protons instead of photons. Treatment with proton therapy can achieve comparable target coverage but significantly reduced doses to critical normal structures, which can lead to fewer predicted SMNs compared with IMRT. By decreasing expected late complications, proton therapy may improve the therapeutic ratio of adjuvant radiation therapy for patients with stage II thymic malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Underwood, Tracy, E-mail: tunderwood@mgh.harvard.edu; Department of Medical Physics and Bioengineering, University College London, London; Giantsoudi, Drosoula

Purpose: For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. Methods and Materials: For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions weremore » simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. Results: Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. Conclusion: If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.« less

A comparison of two prompt gamma imaging techniques with collimator-based cameras for range verification in proton therapy

NASA Astrophysics Data System (ADS)

Lin, Hsin-Hon; Chang, Hao-Ting; Chao, Tsi-Chian; Chuang, Keh-Shih

2017-08-01

In vivo range verification plays an important role in proton therapy to fully utilize the benefits of the Bragg peak (BP) for delivering high radiation dose to tumor, while sparing the normal tissue. For accurately locating the position of BP, camera equipped with collimators (multi-slit and knife-edge collimator) to image prompt gamma (PG) emitted along the proton tracks in the patient have been proposed for range verification. The aim of the work is to compare the performance of multi-slit collimator and knife-edge collimator for non-invasive proton beam range verification. PG imaging was simulated by a validated GATE/GEANT4 Monte Carlo code to model the spot-scanning proton therapy and cylindrical PMMA phantom in detail. For each spot, 108 protons were simulated. To investigate the correlation between the acquired PG profile and the proton range, the falloff regions of PG profiles were fitted with a 3-line-segment curve function as the range estimate. Factors including the energy window setting, proton energy, phantom size, and phantom shift that may influence the accuracy of detecting range were studied. Results indicated that both collimator systems achieve reasonable accuracy and good response to the phantom shift. The accuracy of range predicted by multi-slit collimator system is less affected by the proton energy, while knife-edge collimator system can achieve higher detection efficiency that lead to a smaller deviation in predicting range. We conclude that both collimator systems have potentials for accurately range monitoring in proton therapy. It is noted that neutron contamination has a marked impact on range prediction of the two systems, especially in multi-slit system. Therefore, a neutron reduction technique for improving the accuracy of range verification of proton therapy is needed.

Registration of pencil beam proton radiography data with X-ray CT.

PubMed

Deffet, Sylvain; Macq, Benoît; Righetto, Roberto; Vander Stappen, François; Farace, Paolo

2017-10-01

Proton radiography seems to be a promising tool for assessing the quality of the stopping power computation in proton therapy. However, range error maps obtained on the basis of proton radiographs are very sensitive to small misalignment between the planning CT and the proton radiography acquisitions. In order to be able to mitigate misalignment in postprocessing, the authors implemented a fast method for registration between pencil proton radiography data obtained with a multilayer ionization chamber (MLIC) and an X-ray CT acquired on a head phantom. The registration was performed by optimizing a cost function which performs a comparison between the acquired data and simulated integral depth-dose curves. Two methodologies were considered, one based on dual orthogonal projections and the other one on a single projection. For each methodology, the robustness of the registration algorithm with respect to three confounding factors (measurement noise, CT calibration errors, and spot spacing) was investigated by testing the accuracy of the method through simulations based on a CT scan of a head phantom. The present registration method showed robust convergence towards the optimal solution. For the level of measurement noise and the uncertainty in the stopping power computation expected in proton radiography using a MLIC, the accuracy appeared to be better than 0.3° for angles and 0.3 mm for translations by use of the appropriate cost function. The spot spacing analysis showed that a spacing larger than the 5 mm used by other authors for the investigation of a MLIC for proton radiography led to results with absolute accuracy better than 0.3° for angles and 1 mm for translations when orthogonal proton radiographs were fed into the algorithm. In the case of a single projection, 6 mm was the largest spot spacing presenting an acceptable registration accuracy. For registration of proton radiography data with X-ray CT, the use of a direct ray-tracing algorithm to compute sums of squared differences and corrections of range errors showed very good accuracy and robustness with respect to three confounding factors: measurement noise, calibration error, and spot spacing. It is therefore a suitable algorithm to use in the in vivo range verification framework, allowing to separate in postprocessing the proton range uncertainty due to setup errors from the other sources of uncertainty. © 2017 American Association of Physicists in Medicine.

[Proton imaging applications for proton therapy: state of the art].

PubMed

Amblard, R; Floquet, V; Angellier, G; Hannoun-Lévi, J M; Hérault, J

2015-04-01

Proton therapy allows a highly precise tumour volume irradiation with a low dose delivered to the healthy tissues. The steep dose gradients observed and the high treatment conformity require a precise knowledge of the proton range in matter and the target volume position relative to the beam. Thus, proton imaging allows an improvement of the treatment accuracy, and thereby, in treatment quality. Initially suggested in 1963, radiographic imaging with proton is still not used in clinical routine. The principal difficulty is the lack of spatial resolution, induced by the multiple Coulomb scattering of protons with nuclei. Moreover, its realization for all clinical locations requires relatively high energies that are previously not considered for clinical routine. Abandoned for some time in favor of X-ray technologies, research into new imaging methods using protons is back in the news because of the increase of proton radiation therapy centers in the world. This article exhibits a non-exhaustive state of the art in proton imaging. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org; Henderson, Randal; Pham, Dat

Purpose: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). Methods and Materials: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after justmore » 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. Results: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. Conclusions: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.« less

Can Technological Improvements Reduce the Cost of Proton Radiation Therapy?

PubMed

Schippers, Jacobus Maarten; Lomax, Anthony; Garonna, Adriano; Parodi, Katia

2018-04-01

In recent years there has been increasing interest in the more extensive application of proton therapy in a clinical and preferably hospital-based environment. However, broader adoption of proton therapy has been hindered by the costs of treatment, which are still much higher than those in advanced photon therapy. This article presents an overview of on-going technical developments, which have a reduction of the capital investment or operational costs either as a major goal or as a potential outcome. Developments in instrumentation for proton therapy, such as gantries and accelerators, as well as facility layout and efficiency in treatment logistics will be discussed in this context. Some of these developments are indeed expected to reduce the costs. The examples will show, however, that a dramatic cost reduction of proton therapy is not expected in the near future. Although current developments will certainly contribute to a gradual decrease of the treatment costs in the coming years, many steps will still have to be made to achieve a much lower cost per treatment. Copyright © 2018. Published by Elsevier Inc.

Optimization, Characterization and Commissioning of a Novel Uniform Scanning Proton Beam Delivery System

NASA Astrophysics Data System (ADS)

Mascia, Anthony Edward

Purpose: To develop and characterize the required detectors for uniform scanning optimization and characterization, and to develop the methodology and assess their efficacy for optimizing, characterizing and commissioning a novel proton beam uniform scanning system. Methods and Materials: The Multi Layer Ion Chamber (MLIC), a 1D array of vented parallel plate ion chambers, was developed in-house for measurement of longitudinal profiles. The Matrixx detector (IBA Dosimetry, Germany) and XOmat V film (Kodak, USA) were characterized for measurement of transverse profiles. The architecture of the uniform scanning system was developed and then optimized and characterized for clinical proton radiotherapy. Results: The MLIC detector significantly increased data collection efficiency without sacrificing data quality. The MLIC was capable of integrating an entire scanned and layer stacked proton field with one measurement, producing results with the equivalent spatial sampling of 1.0mm. The Matrixx detector and modified 1D water phantom jig improved data acquisition efficiency and complemented the film measurements. The proximal, central and distal proton field planes were measured using these methods, yielding better than 3% uniformity. The binary range modulator was programmed, optimized and characterized such that the proton field ranges were separated by approximately 5.0mm modulation width and delivered with an accuracy of 1.0mm in water. Several wobbling magnet scan patterns were evaluated and the raster pattern, spot spacing, scan amplitude and overscan margin were optimized for clinical use. Conclusion: Novel detectors and methods are required for clinically efficient optimization and characterization of proton beam scanning systems. Uniform scanning produces proton beam fields that are suited for clinical proton radiotherapy.

WE-D-17A-06: Optically Stimulated Luminescence Detectors as ‘LET-Meters’ in Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Granville, D; Sahoo, N; Sawakuchi, GO

Purpose: To demonstrate and evaluate the potential of optically stimulated luminescence (OSL) detectors (OSLDs) for measurements of linear energy transfer (LET) in therapeutic proton beams. Methods: Batches of Al2O2:C OSLDs were irradiated with an absorbed dose of 0.2 Gy in un-modulated proton beams of varying LET (0.67 keV/μm to 2.58 keV/μm). The OSLDs were read using continuous wave (CW-OSL) and pulsed (P-OSL) stimulation modes. We parameterized and calibrated three characteristics of the OSL signals as functions of LET: CW-OSL curve shape, P-OSL curve shape and the ratio of the two OSL emission band intensities (ultraviolet/blue ratio). Calibration curves were createdmore » for each of these characteristics to describe their behaviors as functions of LET. The true LET values were determined using a validated Monte Carlo model of the proton therapy nozzle used to irradiate the OSLDs. We then irradiated batches of OSLDs with an absorbed dose of 0.2 Gy at various depths in two modulated proton beams (140 MeV, 4 cm wide spread-out Bragg peak (SOBP) and 250 MeV, 10 cm wide SOBP). The LET values were calculated using the OSL response and the calibration curves. Finally, measured LET values were compared to the true values determined using Monte Carlo simulations. Results: The CW-OSL curve shape, P-OSL curve shape and the ultraviolet/blue-ratio provided proton LET estimates within 12.4%, 5.7% and 30.9% of the true values, respectively. Conclusion: We have demonstrated that LET can be measured within 5.7% using Al2O3:C OSLDs in the therapeutic proton beams used in this investigation. From a single OSLD readout, it is possible to measure both the absorbed dose and LET. This has potential future applications in proton therapy quality assurance, particularly for treatment plans based on optimization of LET distributions. This research was partially supported by the Natural Sciences and Engineering Research Council of Canada.« less

Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hata, Masaharu; Miyanaga, Naoto; Tokuuye, Koichi

Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently,more » proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.« less

Future of medical physics: Real-time MRI-guided proton therapy.

PubMed

Oborn, Bradley M; Dowdell, Stephen; Metcalfe, Peter E; Crozier, Stuart; Mohan, Radhe; Keall, Paul J

2017-08-01

With the recent clinical implementation of real-time MRI-guided x-ray beam therapy (MRXT), attention is turning to the concept of combining real-time MRI guidance with proton beam therapy; MRI-guided proton beam therapy (MRPT). MRI guidance for proton beam therapy is expected to offer a compelling improvement to the current treatment workflow which is warranted arguably more than for x-ray beam therapy. This argument is born out of the fact that proton therapy toxicity outcomes are similar to that of the most advanced IMRT treatments, despite being a fundamentally superior particle for cancer treatment. In this Future of Medical Physics article, we describe the various software and hardware aspects of potential MRPT systems and the corresponding treatment workflow. Significant software developments, particularly focused around adaptive MRI-based planning will be required. The magnetic interaction between the MRI and the proton beamline components will be a key area of focus. For example, the modeling and potential redesign of a magnetically compatible gantry to allow for beam delivery from multiple angles towards a patient located within the bore of an MRI scanner. Further to this, the accuracy of pencil beam scanning and beam monitoring in the presence of an MRI fringe field will require modeling, testing, and potential further development to ensure that the highly targeted radiotherapy is maintained. Looking forward we envisage a clear and accelerated path for hardware development, leveraging from lessons learnt from MRXT development. Within few years, simple prototype systems will likely exist, and in a decade, we could envisage coupled systems with integrated gantries. Such milestones will be key in the development of a more efficient, more accurate, and more successful form of proton beam therapy for many common cancer sites. © 2017 American Association of Physicists in Medicine.

SU-D-BRC-04: Development of Proton Tissue Equivalent Materials for Calibration and Dosimetry Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olguin, E; Flampouri, S; Lipnharski, I

Purpose: To develop new proton tissue equivalent materials (PTEM), urethane and fiberglass based, for proton therapy calibration and dosimetry studies. Existing tissue equivalent plastics are applicable only for x-rays because they focus on matching mass attenuation coefficients. This study aims to create new plastics that match mass stopping powers for proton therapy applications instead. Methods: New PTEMs were constructed using urethane and fiberglass resin materials for soft, fat, bone, and lung tissue. The stoichiometric analysis method was first used to determine the elemental composition of each unknown constituent. New initial formulae were then developed for each of the 4 PTEMsmore » using the new elemental compositions and various additives. Samples of each plastic were then created and exposed to a well defined proton beam at the UF Health Proton Therapy Institute (UFHPTI) to validate its mass stopping power. Results: The stoichiometric analysis method revealed the elemental composition of the 3 components used in creating the PTEMs. These urethane and fiberglass based resins were combined with additives such as calcium carbonate, aluminum hydroxide, and phenolic micro spheres to achieve the desired mass stopping powers and densities. Validation at the UFHPTI revealed adjustments had to be made to the formulae, but the plastics eventually had the desired properties after a few iterations. The mass stopping power, density, and Hounsfield Unit of each of the 4 PTEMs were within acceptable tolerances. Conclusion: Four proton tissue equivalent plastics were developed: soft, fat, bone, and lung tissue. These plastics match each of the corresponding tissue’s mass stopping power, density, and Hounsfield Unit, meaning they are truly tissue equivalent for proton therapy applications. They can now be used to calibrate proton therapy treatment planning systems, improve range uncertainties, validate proton therapy Monte Carlo simulations, and assess in-field and out-of-field organ doses.« less

Minibeam therapy with protons and light ions: physical feasibility and potential to reduce radiation side effects and to facilitate hypofractionation.

PubMed

Dilmanian, F Avraham; Eley, John G; Krishnan, Sunil

2015-06-01

Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulations were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage. Copyright © 2015 Elsevier Inc. All rights reserved.

Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer.

PubMed

Huang, Qijie; Jabbour, Salma K; Xiao, Zhiyan; Yue, Ning; Wang, Xiao; Cao, Hongbin; Kuang, Yu; Zhang, Yin; Nie, Ke

2018-04-25

The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy. Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues. Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met. Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Tatsuya; Widder, Joachim; Dijk, Lisanne V. van

2016-11-01

Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Methods and Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2.more » The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D{sub 2} − D{sub 98}, where D{sub 2} and D{sub 98} are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. Results: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. Conclusions: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters.« less

High resolution Cerenkov light imaging of induced positron distribution in proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Seiichi, E-mail: s-yama@met.nagoya-u.ac.jp; Fujii, Kento; Morishita, Yuki

2014-11-01

Purpose: In proton therapy, imaging of the positron distribution produced by fragmentation during or soon after proton irradiation is a useful method to monitor the proton range. Although positron emission tomography (PET) is typically used for this imaging, its spatial resolution is limited. Cerenkov light imaging is a new molecular imaging technology that detects the visible photons that are produced from high-speed electrons using a high sensitivity optical camera. Because its inherent spatial resolution is much higher than PET, the authors can measure more precise information of the proton-induced positron distribution with Cerenkov light imaging technology. For this purpose, theymore » conducted Cerenkov light imaging of induced positron distribution in proton therapy. Methods: First, the authors evaluated the spatial resolution of our Cerenkov light imaging system with a {sup 22}Na point source for the actual imaging setup. Then the transparent acrylic phantoms (100 × 100 × 100 mm{sup 3}) were irradiated with two different proton energies using a spot scanning proton therapy system. Cerenkov light imaging of each phantom was conducted using a high sensitivity electron multiplied charge coupled device (EM-CCD) camera. Results: The Cerenkov light’s spatial resolution for the setup was 0.76 ± 0.6 mm FWHM. They obtained high resolution Cerenkov light images of the positron distributions in the phantoms for two different proton energies and made fused images of the reference images and the Cerenkov light images. The depths of the positron distribution in the phantoms from the Cerenkov light images were almost identical to the simulation results. The decay curves derived from the region-of-interests (ROIs) set on the Cerenkov light images revealed that Cerenkov light images can be used for estimating the half-life of the radionuclide components of positrons. Conclusions: High resolution Cerenkov light imaging of proton-induced positron distribution was possible. The authors conclude that Cerenkov light imaging of proton-induced positron is promising for proton therapy.« less

[Initial clinical experience of proton therapy at Shizuoka Cancer Center].

PubMed

Murayama, Shigeyuki; Fuji, Hiroshi; Yamashita, Haruo; Futami, Yasuyuki; Numano, Masumi; Harada, Hideyuki; Kamata, Minoru; Nishimura, Tetsuo

2005-10-01

To present the initial experience and preliminary clinical results of patients treated mainly with proton irradiation at the newly developed proton therapy facility at Shizuoka Cancer Center. We reviewed 125 patients who underwent proton therapy between July 2003 and December 2004. Of these 125 patients, 11 had head and neck malignancies, 15 non-small cell lung cancers, 22 hepatocellular carcinomas, 62 prostate cancers, and 15 other malignant tumors. Most patients experienced Grade 0-1 acute morbidities (NCI-CTC) in skin or mucosa, while a temporary Grade 2-3 reaction was observed in a high dose area. Response rates were 73% for H & N malignancies, 100% for NSCLC, and 77% for HCC. PSA evaluation for patients with prostate cancer revealed a high rate of complete response. The efficacy and safety of proton therapy at Shizuoka Cancer Center was demonstrated for patients with early-stage cancer or locally advanced disease.

Nanoscale measurements of proton tracks using fluorescent nuclear track detectors

PubMed Central

Sawakuchi, Gabriel O.; Ferreira, Felisberto A.; McFadden, Conor H.; Hallacy, Timothy M.; Granville, Dal A.; Sahoo, Narayan; Akselrod, Mark S.

2016-01-01

Purpose: The authors describe a method in which fluorescence nuclear track detectors (FNTDs), novel track detectors with nanoscale spatial resolution, are used to determine the linear energy transfer (LET) of individual proton tracks from proton therapy beams by allowing visualization and 3D reconstruction of such tracks. Methods: FNTDs were exposed to proton therapy beams with nominal energies ranging from 100 to 250 MeV. Proton track images were then recorded by confocal microscopy of the FNTDs. Proton tracks in the FNTD images were fit by using a Gaussian function to extract fluorescence amplitudes. Histograms of fluorescence amplitudes were then compared with LET spectra. Results: The authors successfully used FNTDs to register individual proton tracks from high-energy proton therapy beams, allowing reconstruction of 3D images of proton tracks along with delta rays. The track amplitudes from FNTDs could be used to parameterize LET spectra, allowing the LET of individual proton tracks from therapeutic proton beams to be determined. Conclusions: FNTDs can be used to directly visualize proton tracks and their delta rays at the nanoscale level. Because the track intensities in the FNTDs correlate with LET, they could be used further to measure LET of individual proton tracks. This method may be useful for measuring nanoscale radiation quantities and for measuring the LET of individual proton tracks in radiation biology experiments. PMID:27147359

Nanoscale measurements of proton tracks using fluorescent nuclear track detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sawakuchi, Gabriel O., E-mail: gsawakuchi@mdanderson.org; Sahoo, Narayan; Ferreira, Felisberto A.

Purpose: The authors describe a method in which fluorescence nuclear track detectors (FNTDs), novel track detectors with nanoscale spatial resolution, are used to determine the linear energy transfer (LET) of individual proton tracks from proton therapy beams by allowing visualization and 3D reconstruction of such tracks. Methods: FNTDs were exposed to proton therapy beams with nominal energies ranging from 100 to 250 MeV. Proton track images were then recorded by confocal microscopy of the FNTDs. Proton tracks in the FNTD images were fit by using a Gaussian function to extract fluorescence amplitudes. Histograms of fluorescence amplitudes were then compared withmore » LET spectra. Results: The authors successfully used FNTDs to register individual proton tracks from high-energy proton therapy beams, allowing reconstruction of 3D images of proton tracks along with delta rays. The track amplitudes from FNTDs could be used to parameterize LET spectra, allowing the LET of individual proton tracks from therapeutic proton beams to be determined. Conclusions: FNTDs can be used to directly visualize proton tracks and their delta rays at the nanoscale level. Because the track intensities in the FNTDs correlate with LET, they could be used further to measure LET of individual proton tracks. This method may be useful for measuring nanoscale radiation quantities and for measuring the LET of individual proton tracks in radiation biology experiments.« less

TH-D-BRC-01: Panel Member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aydogan, B.

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

TH-D-BRC-02: Panel Member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, S.

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

TH-D-BRC-04: Panel Member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, C.

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

TH-D-BRC-03: Panel Member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paganetti, H.

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wei, E-mail: Liu.Wei@mayo.edu; Schild, Steven E.; Chang, Joe Y.

Purpose: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods and Materials: IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered.more » In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. Results: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D{sub 95%} CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D{sub 5%}-D{sub 95%} CTV: 10.3 vs 17.7, resspectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D{sub 95%} CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions: Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions.« less

Investigating the Implications of a Variable RBE on Proton Dose Fractionation Across a Clinical Pencil Beam Scanned Spread-Out Bragg Peak

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, Thomas I.; Chaudhary, Pankaj; Michaelidesová, Anna

2016-05-01

Purpose: To investigate the clinical implications of a variable relative biological effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in linear energy transfer (LET) in the distal regions of the spread-out Bragg peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios are still limited. Methods and Materials: Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfractionmore » period of 24 hours at Proton Therapy Center in Prague, Czech Republic. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a linear quadratic formalism. Results: Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a linear quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens. Conclusions: The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used by the modeling community for the optimization of fractionated proton therapy.« less

Comparison of cellular lethality in DNA repair-proficient or -deficient cell lines resulting from exposure to 70 MeV/n protons or 290 MeV/n carbon ions.

PubMed

Genet, Stefan C; Maeda, Junko; Fujisawa, Hiroshi; Yurkon, Charles R; Fujii, Yoshihiro; Romero, Ashley M; Genik, Paula C; Fujimori, Akira; Kitamura, Hisashi; Kato, Takamitsu A

2012-11-01

Charged particle therapy utilizing protons or carbon ions has been rapidly intensifying over recent years. The present study was designed to jointly investigate these two charged particle treatment modalities with respect to modeled anatomical depth-dependent dose and linear energy transfer (LET) deliveries to cells with either normal or compromised DNA repair phenotypes. We compared cellular lethality in response to dose, LET and Bragg peak location for accelerated protons and carbon ions at 70 and 290 MeV/n, respectively. A novel experimental live cell irradiation OptiCell™ in vitro culture system using three different Chinese hamster ovary (CHO) cells as a mammalian model was conducted. A wild-type DNA repair-competent CHO cell line (CHO 10B2) was compared to two other CHO cell lines (51D1 and xrs5), each genetically deficient with respect to one of the two major DNA repair pathways (homologous recombination and non-homologous end joining pathways, respectively) following genotoxic insults. We found that wild-type and homologous recombination-deficient (Rad51D) cellular lethality was dependent on both the dose and LET of the carbon ions, whereas it was only dependent on dose for protons. The non-homologous end joining deficient cell line (Ku80 mutant) showed nearly identical dose-response profiles for both carbon ions and protons. Our results show that the increasingly used modality of carbon ions as charged particle therapy is advantageous to protons in a radiotherapeutic context, primarily for tumor cells proficient in non-homologous end joining DNA repair where cellular lethality is dependent not only on the dose as in the case of more common photon therapeutic modalities, but more importantly on the carbon ion LETs. Genetic characterization of patient tumors would be key to individualize and optimize the selection of radiation modality, clinical outcome and treatment cost.

Review of medical radiography and tomography with proton beams

NASA Astrophysics Data System (ADS)

Johnson, Robert P.

2018-01-01

The use of hadron beams, especially proton beams, in cancer radiotherapy has expanded rapidly in the past two decades. To fully realize the advantages of hadron therapy over traditional x-ray and gamma-ray therapy requires accurate positioning of the Bragg peak throughout the tumor being treated. A half century ago, suggestions had already been made to use protons themselves to develop images of tumors and surrounding tissue, to be used for treatment planning. The recent global expansion of hadron therapy, coupled with modern advances in computation and particle detection, has led several collaborations around the world to develop prototype detector systems and associated reconstruction codes for proton computed tomography (pCT), as well as more simple proton radiography, with the ultimate intent to use such systems in clinical treatment planning and verification. Recent imaging results of phantoms in hospital proton beams are encouraging, but many technical and programmatic challenges remain to be overcome before pCT scanners will be introduced into clinics. This review introduces hadron therapy and the perceived advantages of pCT and proton radiography for treatment planning, reviews its historical development, and discusses the physics related to proton imaging, the associated experimental and computation issues, the technologies used to attack the problem, contemporary efforts in detector and computational development, and the current status and outlook.

Radiotherapy for Vestibular Schwannomas: A Critical Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, Erin S., E-mail: murphye3@ccf.or; Suh, John H.

2011-03-15

Vestibular schwannomas are slow-growing tumors of the myelin-forming cells that cover cranial nerve VIII. The treatment options for patients with vestibular schwannoma include active observation, surgical management, and radiotherapy. However, the optimal treatment choice remains controversial. We have reviewed the available data and summarized the radiotherapeutic options, including single-session stereotactic radiosurgery, fractionated conventional radiotherapy, fractionated stereotactic radiotherapy, and proton beam therapy. The comparisons of the various radiotherapy modalities have been based on single-institution experiences, which have shown excellent tumor control rates of 91-100%. Both stereotactic radiosurgery and fractionated stereotactic radiotherapy have successfully improved cranial nerve V and VII preservation tomore » >95%. The mixed data regarding the ideal hearing preservation therapy, inherent biases in patient selection, and differences in outcome analysis have made the comparison across radiotherapeutic modalities difficult. Early experience using proton therapy for vestibular schwannoma treatment demonstrated local control rates of 84-100% but disappointing hearing preservation rates of 33-42%. Efforts to improve radiotherapy delivery will focus on refined dosimetry with the goal of reducing the dose to the critical structures. As future randomized trials are unlikely, we suggest regimented pre- and post-treatment assessments, including validated evaluations of cranial nerves V, VII, and VIII, and quality of life assessments with long-term prospective follow-up. The results from such trials will enhance the understanding of therapy outcomes and improve our ability to inform patients.« less

Accurate Monte Carlo simulations for nozzle design, commissioning and quality assurance for a proton radiation therapy facility.

PubMed

Paganetti, H; Jiang, H; Lee, S Y; Kooy, H M

2004-07-01

Monte Carlo dosimetry calculations are essential methods in radiation therapy. To take full advantage of this tool, the beam delivery system has to be simulated in detail and the initial beam parameters have to be known accurately. The modeling of the beam delivery system itself opens various areas where Monte Carlo calculations prove extremely helpful, such as for design and commissioning of a therapy facility as well as for quality assurance verification. The gantry treatment nozzles at the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital (MGH) were modeled in detail using the GEANT4.5.2 Monte Carlo code. For this purpose, various novel solutions for simulating irregular shaped objects in the beam path, like contoured scatterers, patient apertures or patient compensators, were found. The four-dimensional, in time and space, simulation of moving parts, such as the modulator wheel, was implemented. Further, the appropriate physics models and cross sections for proton therapy applications were defined. We present comparisons between measured data and simulations. These show that by modeling the treatment nozzle with millimeter accuracy, it is possible to reproduce measured dose distributions with an accuracy in range and modulation width, in the case of a spread-out Bragg peak (SOBP), of better than 1 mm. The excellent agreement demonstrates that the simulations can even be used to generate beam data for commissioning treatment planning systems. The Monte Carlo nozzle model was used to study mechanical optimization in terms of scattered radiation and secondary radiation in the design of the nozzles. We present simulations on the neutron background. Further, the Monte Carlo calculations supported commissioning efforts in understanding the sensitivity of beam characteristics and how these influence the dose delivered. We present the sensitivity of dose distributions in water with respect to various beam parameters and geometrical misalignments. This allows the definition of tolerances for quality assurance and the design of quality assurance procedures.

Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints

NASA Astrophysics Data System (ADS)

Polster, Lisa; Schuemann, Jan; Rinaldi, Ilaria; Burigo, Lucas; McNamara, Aimee L.; Stewart, Robert D.; Attili, Andrea; Carlson, David J.; Sato, Tatsuhiko; Ramos Méndez, José; Faddegon, Bruce; Perl, Joseph; Paganetti, Harald

2015-07-01

The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients. TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer, while the others are based on DNA double strand break induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments. The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells. This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models.

Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints

PubMed Central

Polster, Lisa; Schuemann, Jan; Rinaldi, Ilaria; Burigo, Lucas; McNamara, Aimee L.; Stewart, Robert D.; Attili, Andrea; Carlson, David J.; Sato, Tatsuhiko; Méndez, José Ramos; Faddegon, Bruce; Perl, Joseph; Paganetti, Harald

2015-01-01

The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients. TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer (LET), while the others are based on DNA Double Strand Break (DSB) induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments. The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells. This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models. PMID:26061666

Study of low energy neutron beam formation based on GEANT4 simulations

NASA Astrophysics Data System (ADS)

Avagyan, R.; Avetisyan, R.; Ivanyan, V.; Kerobyan, I.

2017-07-01

The possibility of obtaining thermal/epithermal energy neutron beams using external protons from cyclotron C18/18 is studied based on GEANT4 simulations. This study will be the basis of the Beam Shaped Assembly (BSA) development for future Boron Neutron Capture Therapy (BNCT). Proton induced reactions on 9Be target are considered as a neutron source, and dependence of neutron yield on target thickness is investigated. The problem of reducing the ratio of gamma to neutron yields by inserting a lead sheet after the beryllium target is studied as well. By GEANT4 modeling the optimal thicknesses of 9Be target and lead absorber are determined and the design characteristics of beam shaping assembly, including the materials and thicknesses of reflector and moderator are considered.

Potential proton beam therapy for recurrent endometrial cancer in the vagina.

PubMed

Yanazume, Shintaro; Arimura, Takeshi; Kobayashi, Hiroaki; Douchi, Tsutomu

2015-05-01

Proton beam radiotherapy mainly has been used in the gynecological field in patients with cervical cancer. The efficacy of proton beam therapy in patients with recurrent endometrial cancer has not yet been determined. A 77-year-old endometrial cancer patient presented with recurrence in the vagina without distant metastasis following hysterectomy. A hard mass measuring 6 cm originated from the apex of the vagina, surrounded the vaginal cavity, and infiltrated the proximal and distal vagina. The patient received proton beam radiotherapy using a less invasive particle treatment system while minimizing the dose to the surrounding normal tissues. The dose to the planning target volume was 74 Gy (relative biological effectiveness) with 37 fractions. The patient was treated with 150-210-MeV proton beams for 53 days. Proton beam therapy led to the disappearance of tumors without any complications except for grade 1 cystitis although evidence of further complications is not available past our 6-month follow-up period. Proton beam therapy may become a useful treatment modality for recurrent endometrial cancer as well as cervical uterine cancer. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Technique for comprehensive head and neck irradiation using 3-dimensional conformal proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, IN; Walter, Alexander S.

2015-01-01

Owing to the technical and logistical complexities of matching photon and proton treatment modalities, we developed and implemented a technique of comprehensive head and neck radiation using 3-dimensional (3D) conformal proton therapy. A monoisocentric technique was used with a 30-cm snout. Cervical lymphatics were treated with 3 fields: a posterior-anterior field with a midline block and a right and a left posterior oblique field. The matchline of the 3 cervical nodal fields with the primary tumor site fields was staggered by 0.5 cm. Comparative intensity-modulated photon plans were later developed for 12 previously treated patients to provide equivalent target coverage,more » while matching or improving on the proton plans' sparing of organs at risk (OARs). Dosimetry to OARs was evaluated and compared by treatment modality. Comprehensive head and neck irradiation using proton therapy yielded treatment plans with significant dose avoidance of the oral cavity and midline neck structures. When compared with the generated intensity-modulated radiation therapy (IMRT) plans, the proton treatment plans yielded statistically significant reductions in the mean and integral radiation dose to the oral cavity, larynx, esophagus, and the maximally spared parotid gland. There was no significant difference in mean dose to the lesser-spared parotid gland by treatment modality or in mean or integral dose to the spared submandibular glands. A technique for cervical nodal irradiation using 3D conformal proton therapy with uniform scanning was developed and clinically implemented. Use of proton therapy for cervical nodal irradiation resulted in large volume of dose avoidance to the oral cavity and low dose exposure to midline structures of the larynx and the esophagus, with lower mean and integral dose to assessed OARs when compared with competing IMRT plans.« less

Early Clinical Outcomes Using Proton Radiation for Children With Central Nervous System Atypical Teratoid Rhabdoid Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Amorim Bernstein, Karen; Sethi, Roshan; Trofimov, Alexei

2013-05-01

Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive tumor that often affects infants. Irradiation improves survival but has traditionally been avoided in patients under the age of 3 due to the increasing risk of neurocognitive side effects. We report the first cohort of AT/RT patients treated with proton therapy. Methods and Materials: All patients with AT/RT treated at Massachusetts General Hospital (MGH) Frances H. Burr Proton Beam Therapy Benter between July 2004 and November 2011 were included in this study. All patients were treated with 3-dimensional conformal proton therapy (3D-CPT). Results: Ten consecutive patients of a median 2.3more » years of age and with a median follow-up of 27.3 months (range, 11.3-99.4 months) were identified. Two patients suffered distant relapse; 1 patient was successfully treated with involved field irradiation and chemotherapy, while the second patient died of disease. At last follow-up, 9 patients were alive without evidence of disease. Proton radiation demonstrated increasing sparing of the cerebrum, temporal lobe, cochlea, and hypothalamus. Conclusions: Initial clinical outcomes with proton therapy are favorable. The advantages of proton therapy are particularly suited to the treatment of AT/RT, a tumor that often requires irradiation treatment at an age when avoiding irradiation to healthy tissues is most desirable.« less

The GEANT4 toolkit capability in the hadron therapy field: simulation of a transport beam line

NASA Astrophysics Data System (ADS)

Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Raffaele, L.; Russo, G.; Guatelli, S.; Pia, M. G.

2006-01-01

At Laboratori Nazionali del Sud of the Instituto Nazionale di Fisica Nucleare of Catania (Sicily, Italy), the first Italian hadron therapy facility named CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) has been realized. Inside CATANA 62 MeV proton beams, accelerated by a superconducting cyclotron, are used for the radiotherapeutic treatments of some types of ocular tumours. Therapy with hadron beams still represents a pioneer technique, and only a few centers worldwide can provide this advanced specialized cancer treatment. On the basis of the experience so far gained, and considering the future hadron-therapy facilities to be developed (Rinecker, Munich Germany, Heidelberg/GSI, Darmstadt, Germany, PSI Villigen, Switzerland, CNAO, Pavia, Italy, Centro di Adroterapia, Catania, Italy) we decided to develop a Monte Carlo application based on the GEANT4 toolkit, for the design, the realization and the optimization of a proton-therapy beam line. Another feature of our project is to provide a general tool able to study the interactions of hadrons with the human tissue and to test the analytical-based treatment planning systems actually used in the routine practice. All the typical elements of a hadron-therapy line, such as diffusers, range shifters, collimators and detectors were modelled. In particular, we simulated the Markus type ionization chamber and a Gaf Chromic film as dosimeters to reconstruct the depth (Bragg peak and Spread Out Bragg Peak) and lateral dose distributions, respectively. We validated our simulated detectors comparing the results with the experimental data available in our facility.

Low-dose or standard-dose proton pump inhibitors for maintenance therapy of gastro-oesophageal reflux disease: a cost-effectiveness analysis.

PubMed

You, J H S; Lee, A C M; Wong, S C Y; Chan, F K L

2003-03-15

Studies on the use of low-dose proton pump inhibitor for the maintenance therapy of gastro-oesophageal reflux disease have shown that it might be comparable with standard-dose proton pump inhibitor treatment and superior to standard-dose histamine-2 receptor antagonist therapy. To compare the impact of standard-dose histamine-2 receptor antagonist, low-dose proton pump inhibitor and standard-dose proton pump inhibitor treatment for the maintenance therapy of gastro-oesophageal reflux disease on symptom control and health care resource utilization from the perspective of a public health organization in Hong Kong. A Markov model was designed to simulate, over 12 months, the economic and clinical outcomes of gastro-oesophageal reflux disease patients treated with standard-dose histamine-2 receptor antagonist, low-dose proton pump inhibitor and standard-dose proton pump inhibitor. The transition probabilities were derived from the literature. Resource utilization was retrieved from a group of gastro-oesophageal reflux disease patients in Hong Kong. Sensitivity analysis was conducted to examine the robustness of the model. The standard-dose proton pump inhibitor strategy was associated with the highest numbers of symptom-free patient-years (0.954 years) and quality-adjusted life-years gained (0.999 years), followed by low-dose proton pump inhibitor and standard-dose histamine-2 receptor antagonist. The direct medical cost per patient in the standard-dose proton pump inhibitor group (904 US dollars) was lower than those of the low-dose proton pump inhibitor and standard-dose histamine-2 receptor antagonist groups. The standard-dose proton pump inhibitor strategy appears to be the most effective and least costly for the maintenance management of patients with gastro-oesophageal reflux disease in Hong Kong.

Hadron Cancer Therapy: Role of Nuclear Reactions

DOE R&D Accomplishments Database

Chadwick, M. B.

2000-06-20

Recently it has become feasible to calculate energy deposition and particle transport in the body by proton and neutron radiotherapy beams, using Monte Carlo transport methods. A number of advances have made this possible, including dramatic increases in computer speeds, a better understanding of the microscopic nuclear reaction cross sections, and the development of methods to model the characteristics of the radiation emerging from the accelerator treatment unit. This paper describes the nuclear reaction mechanisms involved, and how the cross sections have been evaluated from theory and experiment, for use in computer simulations of radiation therapy. The simulations will allow the dose delivered to a tumor to be optimized, whilst minimizing the dos given to nearby organs at risk.

The Francis H. Burr Proton Therapy Center

NASA Astrophysics Data System (ADS)

Flanz, Jay; Kooy, Hanne; DeLaney, Thomas F.

The Francis H. Burr Proton Therapy Center (FHBPTC) is one of the first hospital-based proton therapy (PT) facilities. Its development was the natural evolution of several decades of PT experience of the Massachusetts General Hospital treating patients at the Harvard Cyclotron Laboratory. The operations of the FHBPTC reflect the combined missions of patient care, clinical and physics research, technological developments, and education. This chapter will discuss aspects of the history, evolution, and performance of this unique PT center.

Incidence of Second Malignancies Among Patients Treated With Proton Versus Photon Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Christine S., E-mail: chungc1@sutterhealth.org; Yock, Torunn I.; Nelson, Kerrie

2013-09-01

Purpose: Proton radiation, when compared with photon radiation, allows delivery of increased radiation dose to the tumor while decreasing dose to adjacent critical structures. Given the recent expansion of proton facilities in the United States, the long-term sequelae of proton therapy should be carefully assessed. The objective of this study was to compare the incidence of second cancers in patients treated with proton radiation with a population-based cohort of matched patients treated with photon radiation. Methods and Materials: We performed a retrospective cohort study of 558 patients treated with proton radiation from 1973 to 2001 at the Harvard Cyclotron inmore » Cambridge, MA and 558 matched patients treated with photon therapy in the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry. Patients were matched by age at radiation treatment, sex, year of treatment, cancer histology, and site. The main outcome measure was the incidence of second malignancies after radiation. Results: We matched 558 proton patients with 558 photon patients from the Surveillance, Epidemiology, and End Results registry. The median duration of follow-up was 6.7 years (interquartile range, 7.4) and 6.0 years (interquartile range, 9.3) in the proton and photon cohorts, respectively. The median age at treatment was 59 years in each cohort. Second malignancies occurred in 29 proton patients (5.2%) and 42 photon patients (7.5%). After we adjusted for sex, age at treatment, primary site, and year of diagnosis, proton therapy was not associated with an increased risk of second malignancy (adjusted hazard ratio, 0.52 [95% confidence interval, 0.32-0.85]; P=.009). Conclusions: The use of proton radiation therapy was not associated with a significantly increased risk of secondary malignancies compared with photon therapy. Longer follow-up of these patients is needed to determine if there is a significant decrease in second malignancies. Given the limitations of the study, these results should be viewed as hypothesis generating.« less

Project of the demonstration center of proton therapy at DLNP JINR

NASA Astrophysics Data System (ADS)

Syresin, E. M.; Bokor, J.; Breev, V. M.; Karamysheva, G. A.; Kazarinov, M. Yu.; Morozov, N. A.; Mytsin, G. V.; Shakun, N. G.; Shvidky, S. V.; Shirkov, G. D.

2015-07-01

JINR is one of the leading research centers of proton therapy in Russia. The modern technique of 3D conformal proton radiotherapy was first effectuated in Russia in this center, and now it is effectively used in regular treatment sessions. A special Medial Technical Complex (MTC) was created at JINR on the basis of a phasotron used for proton treatment. About 100 patients undergo a course of fractionated treatment here every year. Over the last 14 years since the startup of the Dubna radiological department, more than 1000 patients have been treated by protons. The project of the demonstration center of proton therapy is proposed on the basis of a superconducting 230 MeV synchrocyclotron S2C2 of new IBA compact proton system Proteus ONE. The superconducting synchrocyclotron is planned to for instillation instead of a phasotron in the Medical Technical Complex, DLNP. For the demonstration center, a new transport line will be designed for beam delivery to the medical cabin.

Dosimetric Comparison of Combined Intensity-Modulated Radiotherapy (IMRT) and Proton Therapy Versus IMRT Alone for Pelvic and Para-Aortic Radiotherapy in Gynecologic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berman Milby, Abigail; Both, Stefan, E-mail: both@uphs.upenn.edu; Ingram, Mark

2012-03-01

Purpose: To perform a dosimetric comparison of intensity-modulated radiotherapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT) to the para-aortic (PA) nodal region in women with locally advanced gynecologic malignancies. Methods and Materials: The CT treatment planning scans of 10 consecutive patients treated with IMRT to the pelvis and PA nodes were identified. The clinical target volume was defined by the primary tumor for patients with cervical cancer and by the vagina and paravaginal tissues for patients with endometrial cancer, in addition to the regional lymph nodes. The IMRT, PSPT, and IMPT plans were generated using themore » Eclipse Treatment Planning System and were analyzed for various dosimetric endpoints. Two groups of treatment plans including proton radiotherapy were created: IMRT to pelvic nodes with PSPT to PA nodes (PSPT/IMRT), and IMRT to pelvic nodes with IMPT to PA nodes (IMPT/IMRT). The IMRT and proton RT plans were optimized to deliver 50.4 Gy or Gy (relative biologic effectiveness [RBE)), respectively. Dose-volume histograms were analyzed for all of the organs at risk. The paired t test was used for all statistical comparison. Results: The small-bowel V{sub 20}, V{sub 30}, V{sub 35}, andV{sub 40} were reduced in PSPT/IMRT by 11%, 18%, 27%, and 43%, respectively (p < 0.01). Treatment with IMPT/IMRT demonstrated a 32% decrease in the small-bowel V{sub 20}. Treatment with PSPT/IMRT showed statistically significant reductions in the body V{sub 5-20}; IMPT/IMRT showed reductions in the body V{sub 5-15}. The dose received by half of both kidneys was reduced by PSPT/IMRT and by IMPT/IMRT. All plans maintained excellent coverage of the planning target volume. Conclusions: Compared with IMRT alone, PSPT/IMRT and IMPT/IMRT had a statistically significant decrease in dose to the small and large bowel and kidneys, while maintaining excellent planning target volume coverage. Further studies should be done to correlate the clinical significance of these findings.« less

Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer.

PubMed

Hayashi, Yuichiro; Nakamura, Tatsuya; Mitsudo, Kenji; Kimura, Kanako; Yamaguchi, Hisashi; Ono, Takashi; Azami, Yusuke; Takayama, Kanako; Hirose, Katsumi; Yabuuchi, Tomonori; Suzuki, Motohisa; Hatayama, Yoshiomi; Kikuchi, Yasuhiro; Wada, Hitoshi; Fuwa, Nobukazu; Hareyama, Masato; Tohnai, Iwai

2017-10-01

The purpose of this study was to clarify the efficacy and toxicities of re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer. Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra-arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan. For all patients, the median follow-up was 25 months (range, 3-77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One-year and 2-year overall survival (OS) rates were 62% and 42%, respectively. One-year and 2-year LC rates were 77% and 60%, respectively. No treatment-related deaths were observed during the treatment and follow-up periods. Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer. © 2016 John Wiley & Sons Australia, Ltd.

Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bush, David A., E-mail: dbush@llu.edu; Smith, Jason C.; Slater, Jerry D.

2016-05-01

Purpose: To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC). Methods and Materials: Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractionsmore » over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization. Results: At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group. Conclusions: This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are significantly fewer hospitalization days after proton treatment, which may indicate reduced toxicity with proton beam therapy.« less

Laser Focus

ERIC Educational Resources Information Center

Stuart, Reginald

2011-01-01

Hampton University President William Harvey's initial readings of proton therapy for cancer sparked his interest. Within a few months, Dr. Harvey was assigning widely respected Hampton nuclear physicist Dr. Cynthia Keppel to do more exploration. Today, the new $225 million Hampton University Proton Therapy Institute, one of eight therapy sites in…

Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: a dosimetric study.

PubMed

Welsh, James; Gomez, Daniel; Palmer, Matthew B; Riley, Beverly A; Mayankkumar, Amin V; Komaki, Ritsuko; Dong, Lei; Zhu, X Ronald; Likhacheva, Anna; Liao, Zhongxing; Hofstetter, Wayne L; Ajani, Jaffer A; Cox, James D

2011-12-01

We have previously found that ≤ 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p<.0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p≤.0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p<.001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p≤.02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p<.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p≤.005), heart (p≤.003), and liver (p≤.04). Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigated further in a prospective trial at our institution. Copyright © 2011 Elsevier Inc. All rights reserved.

TU-FG-BRB-04: A New Optimization Method for Pre-Treatment Patient-Specific Stopping-Power by Combining Proton Radiography and X-Ray CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins-Fekete, C; Centre Hospitalier University de Quebec, Quebec, QC; Mass General Hospital

Purpose: The relative stopping power (RSP) uncertainty is the largest contributor to the range uncertainty in proton therapy. The purpose of this work is to develop a robust and systematic method that yields accurate patient specific RSPs by combining pre-treatment X-ray CT and daily proton radiography. Methods: The method is formulated as a penalized least squares optimization (PLSO) problem min(|Ax-B|). The matrix A represents the cumulative path-length crossed in each material computed by calculating proton trajectories through the X-ray CT. The material RSPs are denoted by x and B is the pRad, expressed as water equivalent thickness. The equation ismore » solved using a convex-conic optimizer. Geant4 simulations were made to assess the feasibility of the method. RSP extracted from the Geant4 materials were used as a reference and the clinical HU-RSP curve as a comparison. The PLSO was first tested on a Gammex RMI-467 phantom. Then, anthropomorphic phantoms of the head, pelvis and lung were studied and resulting RSPs were evaluated. A pencil beam was generated in each phantom to evaluate the proton range accuracy achievable by using the optimized RSPs. Finally, experimental data of a pediatric head phantom (CIRS) were acquired using a recently completed experimental pCT scanner. Results: Numerical simulations showed precise RSP (<0.75%) for Gammex materials except low-density lung (LN-300) (1.2%). Accurate RSP have been obtained for the head (µ=−0.10%, 1.5σ=1.12%), lung (µ=−0.33, 1.5σ=1.02%) and pelvis anthropomorphic phantoms (µ=0.12, 1.5σ=0,99%). The range precision has been improved with an average R80 difference to the reference (µ±1.5σ) of −0.20±0.35%, −0.47±0.92% and −0.06±0.17% in the head, lung and pelvis phantoms respectively, compared to the 3.5% clinical margin. Experimental HU-RSP curve have been produced on the CIRS pediatric head. Conclusion: The proposed PLSO with prior knowledge X-ray CT shows promising potential (R80 σ<1.0% over all sites) to decrease the range uncertainty.« less

WE-G-BRE-04: Gold Nanoparticle Induced Vasculature Damage for Proton Therapy: Monte Carlo Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Y; Paganetti, H; Schuemann, J

2014-06-15

Purpose: The aim of this work is to investigate the gold nanoparticle (GNP) induced vasculature damage in a proton beam. We compared the results using a clinical proton beam, 6MV photon beam and two kilovoltage photon beams. Methods: Monte Carlo simulations were carried out using TOPAS (TOol for PArticle Simulation) to obtain the spatial dose distribution in close proximity to GNPs up to 20μm distance. The spatial dose distribution was used as an input to calculate the additional dose deposited to the blood vessels. For this study, GNP induced vasculature damage is evaluated for three particle sources (proton beam, MVmore » photon beam and kV photon beam), various treatment depths for each particle source, various GNP uptakes and three different vessel diameters (8μm, 14μm and 20μm). Results: The result shows that for kV photon, GNPs induce more dose in the vessel wall for 150kVp photon source than 250kVp. For proton therapy, GNPs cause more dose in the vessel wall at shallower treatment depths. For 6MV photons, GNPs induce more dose in the vessel wall at deeper treatment depths. For the same GNP concentration and prescribed dose, the additional dose at the inner vessel wall is 30% more than the prescribed dose for the kVp photon source, 15% more for the proton source and only 2% more for the 6MV photon source. In addition, the dose from GNPs deceases sharper for proton therapy than kVp photon therapy as the distance from the vessel inner wall increases. Conclusion: We show in this study that GNPs can potentially be used to enhance radiation therapy by causing vasculature damage using clinical proton beams. The GNP induced damage for proton therapy is less than for the kVp photon source but significantly larger than for the clinical MV photon source.« less

MO-FG-CAMPUS-TeP3-01: A Model of Baseline Shift to Improve Robustness of Proton Therapy Treatments of Moving Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souris, K; Barragan Montero, A; Di Perri, D

Purpose: The shift in mean position of a moving tumor also known as “baseline shift”, has been modeled, in order to automatically generate uncertainty scenarios for the assessment and robust optimization of proton therapy treatments in lung cancer. Methods: An average CT scan and a Mid-Position CT scan (MidPCT) of the patient at the planning time are first generated from a 4D-CT data. The mean position of the tumor along the breathing cycle is represented by the GTV contour in the MidPCT. Several studies reported both systematic and random variations of the mean tumor position from fraction to fraction. Ourmore » model can simulate this baseline shift by generating a local deformation field that moves the tumor on all phases of the 4D-CT, without creating any non-physical artifact. The deformation field is comprised of normal and tangential components with respect to the lung wall in order to allow the tumor to slip within the lung instead of deforming the lung surface. The deformation field is eventually smoothed in order to enforce its continuity. Two 4D-CT series acquired at 1 week of interval were used to validate the model. Results: Based on the first 4D-CT set, the model was able to generate a third 4D-CT that reproduced the 5.8 mm baseline-shift measured in the second 4D-CT. Water equivalent thickness (WET) of the voxels have been computed for the 3 average CTs. The root mean square deviation of the WET in the GTV is 0.34 mm between week 1 and week 2, and 0.08 mm between the simulated data and week 2. Conclusion: Our model can be used to automatically generate uncertainty scenarios for robustness analysis of a proton therapy plan. The generated scenarios can also feed a TPS equipped with a robust optimizer. Kevin Souris, Ana Barragan, and Dario Di Perri are financially supported by Televie Grants from F.R.S.-FNRS.« less

Proton Therapy

MedlinePlus

... effects of the treatment. top of page What equipment is used? Proton beam therapy uses special machines, ... tumor cells. top of page Who operates the equipment? With backgrounds in mechanical, electrical, software, hardware and ...

TH-D-BRC-00: Educational Point Counter/Point: Has Photon RT Hit the Limits?

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens

2013-05-15

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposedmore » lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.« less

A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma.

PubMed

Ho, Evangeline S Q; Barrett, Sarah A; Mullaney, Laura M

2017-08-01

Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. Conventional CSI photon therapy (Photon-CSI) delivers significant dose to surrounding normal tissue (NT). Research into pediatric CSI with proton therapy (Proton-CSI) has increased, with the aim of exploiting the potential to reduce NT dose and associated post-treatment complications. This review aims to compare treatment outcomes of pediatric medulloblastoma patients between Proton- and Photon-CSI treatments. A search and review of studies published between 1990 and 2016 comparing pediatric (2-18 years) medulloblastoma Proton- and Photon-CSI in three aspects - normal organ sparing and target coverage; normal organ dysfunction and second malignancy risks - was completed. Fifteen studies were selected for review and the results were directly compared. Proton-CSI reported improved out-of-field organ sparing while target coverage improvements were inconsistent. Normal organ dysfunction risks were predicted to be lower following Proton-CSI. Secondary malignancy risks (SMRs) were generally lower with Proton-CSI based on several different risk models. Proton-CSI conferred better treatment outcomes than Photon-CSI for pediatric medulloblastoma patients. This review serves to compare the current literature in the absence of long-term data from prospective studies.

Proton beam characterization in the experimental room of the Trento Proton Therapy facility

NASA Astrophysics Data System (ADS)

Tommasino, F.; Rovituso, M.; Fabiano, S.; Piffer, S.; Manea, C.; Lorentini, S.; Lanzone, S.; Wang, Z.; Pasini, M.; Burger, W. J.; La Tessa, C.; Scifoni, E.; Schwarz, M.; Durante, M.

2017-10-01

As proton therapy is becoming an established treatment methodology for cancer patients, the number of proton centres is gradually growing worldwide. The economical effort for building these facilities is motivated by the clinical aspects, but might be also supported by the potential relevance for the research community. Experiments with high-energy protons are needed not only for medical physics applications, but represent also an essential part of activities dedicated to detector development, space research, radiation hardness tests, as well as of fundamental research in nuclear and particle physics. Here we present the characterization of the beam line installed in the experimental room of the Trento Proton Therapy Centre (Italy). Measurements of beam spot size and envelope, range verification and proton flux were performed in the energy range between 70 and 228 MeV. Methods for reducing the proton flux from typical treatments values of 106-109 particles/s down to 101-105 particles/s were also investigated. These data confirm that a proton beam produced in a clinical centre build by a commercial company can be exploited for a broad spectrum of experimental activities. The results presented here will be used as a reference for future experiments.

SU-F-T-189: Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takao, S; Matsuzaki, Y; Matsuura, T

Purpose: Spot-scanning technique has been utilized to achieve conformal dose distribution to large and complicated tumors. This technique generally does not require patient-specific devices such as aperture and compensator. The commercially available spot-scanning proton therapy (SSPT) systems, however, cannot deliver proton beams to the region shallower than 4 g/cm2. Therefore some range compensation device is required to treat superficial tumors with SSPT. This study shows dosimetric comparison of the following treatment techniques: (i) with a tabletop bolus, (ii) with a nozzle-mounted applicator, and (iii) without any devices and using intensity-modulated proton therapy (IMPT) technique. Methods: The applicator composed of amore » combination of a mini-ridge filter and a range shifter has been manufactured by Hitachi, Ltd., and the tabletop bolus was made by .decimal, Inc. Both devices have been clinically implemented in our facility. Three patients with liver tumors close to the skin surface were examined in this study. Each treatment plan was optimized so that the prescription dose of 76 Gy(RBE) or 66 Gy(RBE) would be delivered to 99% of the clinical target volume in 20 fractions. Three beams were used for tabletop bolus plan and IMPT plan, whereas two beams were used in the applicator plan because the gantry angle available was limited due to potential collision to patient and couch. The normal liver, colon, and skin were considered as organs at risk (OARs). Results: The target heterogeneity index (HI = D{sub 5}/D{sub 95}) was 1.03 on average in each planning technique. The mean dose to the normal liver was considerably less than 20 Gy(RBE) in all cases. The dose to the skin could be reduced by 20 Gy(RBE) on average in the IMPT plan compared to the applicator plan. Conclusion: It has been confirmed that all treatment techniques met the dosimetric criteria for the OARs and could be implemented clinically.« less

SU-E-T-567: Neutron Dose Equivalent Evaluation for Pencil Beam Scanning Proton Therapy with Apertures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, C; Nanjing University of Aeronautics and Astronautics, Nanjing; Schuemann, J

Purpose: To determine the neutron contamination from the aperture in pencil beam scanning during proton therapy. Methods: A Monte Carlo based proton therapy research platform TOPAS and the UF-series hybrid pediatric phantoms were used to perform this study. First, pencil beam scanning (PBS) treatment pediatric plans with average spot size of 10 mm at iso-center were created and optimized for three patients with and without apertures. Then, the plans were imported into TOPAS. A scripting method was developed to automatically replace the patient CT with a whole body phantom positioned according to the original plan iso-center. The neutron dose equivalentmore » was calculated using organ specific quality factors for two phantoms resembling a 4- and 14-years old patient. Results: The neutron dose equivalent generated by the apertures in PBS is 4–10% of the total neutron dose equivalent for organs near the target, while roughly 40% for organs far from the target. Compared to the neutron dose equivalent caused by PBS without aperture, the results show that the neutron dose equivalent with aperture is reduced in the organs near the target, and moderately increased for those organs located further from the target. This is due to the reduction of the proton dose around the edge of the CTV, which causes fewer neutrons generated in the patient. Conclusion: Clinically, for pediatric patients, one might consider adding an aperture to get a more conformal treatment plan if the spot size is too large. This work shows the somewhat surprising fact that adding an aperture for beam scanning for facilities with large spot sizes reduces instead of increases a potential neutron background in regions near target. Changran Geng is supported by the Chinese Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087)« less

SU-E-T-187: Collimation Methods in Spot Scanning Proton Therapy: A Treatment Plan Comparison Between a Fixed Aperture and a Dynamic Collimation System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, B; Gelover, E; Wang, D

2015-06-15

Purpose: Low-energy treatments during spot scanning proton therapy (SSPT) suffer from poor conformity due to increased spot size. Collimation devices can reduce the lateral penumbra of a proton therapy dose distribution and improve the overall plan quality. The purpose of this work was to study the advantages of individual energy-layer collimation, which is unique to a recently proposed Dynamic Collimation System (DCS), in comparison to a standard, fixed aperture that allows only a single shape for all energy layers. Methods: Three brain patients previously planned and treated with SSPT were re-planned using an in-house treatment planning system capable of modelingmore » collimated and un-collimated proton beamlets. The un-collimated plans, which served as a baseline for comparison, reproduced the target coverage of the clinically delivered plans. The collimator opening for the aperture based plans included a 0.6 cm expansion of the largest cross section of the target in the Beam’s Eye View, while the DCS based plans were created by optimizing the collimator position for beam spots near the periphery of the target in each energy layer. Results: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring, averaged 9.13% and 3.48% for the DCS and aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 16.42% and 8.16% for the DCS and aperture plans, respectively. Conclusion: Collimation reduces the dose to normal tissue adjacent to the target and increases dose conformity to the target region for low-energy SSPT. The ability of the DCS to provide collimation to each energy layer yields better conformity in comparison to fixed aperture plans. This work was partially funded by IBA (Ion Beam Applications S.A.)« less

TU-EF-304-03: 4D Monte Carlo Robustness Test for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souris, K; Sterpin, E; Lee, J

Purpose: Breathing motion and approximate dose calculation engines may increase proton range uncertainties. We address these two issues using a comprehensive 4D robustness evaluation tool based on an efficient Monte Carlo (MC) engine, which can simulate breathing with no significant increase in computation time. Methods: To assess the robustness of the treatment plan, multiple scenarios of uncertainties are simulated, taking into account the systematic and random setup errors, range uncertainties, and organ motion. Our fast MC dose engine, called MCsquare, implements optimized models on a massively-parallel computation architecture and allows us to accurately simulate a scenario in less than onemore » minute. The deviations of the uncertainty scenarios are then reported on a DVH-band and compared to the nominal plan.The robustness evaluation tool is illustrated in a lung case by comparing three 60Gy treatment plans. First, a plan is optimized on a PTV obtained by extending the CTV with an 8mm margin, in order to take into account systematic geometrical uncertainties, like in our current practice in radiotherapy. No specific strategy is employed to correct for tumor and organ motions. The second plan involves a PTV generated from the ITV, which encompasses the tumor volume in all breathing phases. The last plan results from robust optimization performed on the ITV, with robustness parameters of 3% for tissue density and 8 mm for positioning errors. Results: The robustness test revealed that the first two plans could not properly cover the target in the presence of uncertainties. CTV-coverage (D95) in the three plans ranged respectively between 39.4–55.5Gy, 50.2–57.5Gy, and 55.1–58.6Gy. Conclusion: A realistic robustness verification tool based on a fast MC dose engine has been developed. This test is essential to assess the quality of proton therapy plan and very useful to study various planning strategies for mobile tumors. This work is partly funded by IBA (Louvain-la-Neuve, Belgium)« less

Fiducial Marker Placement

MedlinePlus

... such as stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) , or proton therapy . Fiducial markers are small ... Proton Therapy Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT) Images related to Fiducial Marker Placement Sponsored ...

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eley, John G., E-mail: jeley@som.umaryland.edu; University of Texas Graduate School of Biomedical Sciences, Houston, Texas; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland

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 breastmore » 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.« less

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy.

PubMed

Eley, John G; Friedrich, Thomas; Homann, Kenneth L; Howell, Rebecca M; Scholz, Michael; Durante, Marco; Newhauser, Wayne D

2016-05-01

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. 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. 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). 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.

Ambient neutron dose equivalent during proton therapy using wobbling scanning system: Measurements and calculations

NASA Astrophysics Data System (ADS)

Lin, Yung-Chieh; Lee, Chung-Chi; Chao, Tsi-Chian; Tsai, Hui-Yu

2017-11-01

Neutron production is a concern in proton therapy, particularly in scattering proton beam delivery systems. Despite this fact, little is known about the effects of secondary neutron exposure around wobbling scattered proton treatment nozzles. The objective of this study was to estimate the neutron dose level resulting from the use of a wobbling scattered proton treatment unit. We applied the Monte Carlo method for predict the ambient neutron dose equivalent, H*(10), per absorbed dose at the treatment isocenter, D, in the proton therapy center of Chang Gung Memorial Hospital, Linkou, Taiwan. For a 190-MeV proton beam, H* (10) / D values typically decreased with the distance from the isocenter, being 1.106 mSv/Gy at the isocenter versus 0.112 mSv/Gy at a distance of 150 cm from the isocenter. The H* (10) / D values generally decreased as the neutron receptors moved away from the isocenter, and increased when the angle from the initial beam axis increased. The ambient neutron dose equivalents were observed to be slightly lower in the direction of multileaf collimator movement. For radiation protection, the central axis of a proton-treated patient is suggested to be at the 0° angle of the beam. If the beam direction at the 90° angle is necessary, the patient axis is suggested to be along with the direction of MLC movement. Our study provides the neutron dose level and neutron energy fluence for the first wobbling proton system at the proton therapy center of Chang Gung Memorial Hospital.

Proton Radiotherapy for Pediatric Bladder/Prostate Rhabdomyosarcoma: Clinical Outcomes and Dosimetry Compared to Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cotter, Shane E.; Herrup, David A.; Friedmann, Alison

Purpose: In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures. Methods and Materials: Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an IMRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan wasmore » optimized for target coverage and normal tissue sparing. Results: Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11-70 months). Median follow-up was 27 months (10-90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p = 0.03), testes (0.0 CGE vs. 0.6 Gy; p = 0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p = 0.016), growth plates (21.7 CGE vs. 32.4 Gy; p = 0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p = 0.016) compared to IMRT. Conclusions: This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies incorporating extended follow-up, objective outcome measures, and quality-of-life analyses.« less

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PubMed

Liu, Chenbin; Schild, Steven E; Chang, Joe Y; Liao, Zhongxing; Korte, Shawn; Shen, Jiajian; Ding, Xiaoning; Hu, Yanle; Kang, Yixiu; Keole, Sameer R; Sio, Terence T; Wong, William W; Sahoo, Narayan; Bues, Martin; Liu, Wei

2018-06-01

To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large-spot machine, which gives the planning system more freedom to compensate for the higher sensitivity to uncertainties and interplay effects for lung cancer treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer.

PubMed

Colaco, Rovel J; Huh, Soon; Nichols, Romaine C; Morris, Christopher G; D'Agostino, Harry; Flampouri, Stella; Li, Zuofeng; Pham, Dat C; Bajwa, Abubakr A; Hoppe, Bradford S

2013-04-01

Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.

Minibeam Therapy With Protons and Light Ions: Physical Feasibility and Potential to Reduce Radiation Side Effects and to Facilitate Hypofractionation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilmanian, F. Avraham, E-mail: avraham.dilmanian@stonybrook.edu; Eley, John G.; Krishnan, Sunil

2015-06-01

Purpose: Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Methods and Materials: Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulationsmore » were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. Results: A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Conclusions: Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage.« less

Modeling and optimization of a time-resolved proton radiographic imaging system for proton cancer treatment

NASA Astrophysics Data System (ADS)

Han, Bin

This dissertation describes a research project to test the clinical utility of a time-resolved proton radiographic (TRPR) imaging system by performing comprehensive Monte Carlo simulations of a physical device coupled with realistic lung cancer patient anatomy defined by 4DCT for proton therapy. A time-resolved proton radiographic imaging system was modeled through Monte Carlo simulations. A particle-tracking feature was employed to evaluate the performance of the proton imaging system, especially in its ability to visualize and quantify proton range variations during respiration. The Most Likely Path (MLP) algorithm was developed to approximate the multiple Coulomb scattering paths of protons for the purpose of image reconstruction. Spatial resolution of ˜ 1 mm and range resolution of 1.3% of the total range were achieved using the MLP algorithm. Time-resolved proton radiographs of five patient cases were reconstructed to track tumor motion and to calculate water equivalent length variations. By comparing with direct 4DCT measurement, the accuracy of tumor tracking was found to be better than 2 mm in five patient cases. Utilizing tumor tracking information to reduce margins to the planning target volume, a gated treatment plan was compared with un-gated treatment plan. The equivalent uniform dose (EUD) and the normal tissue complication probability (NTCP) were used to quantify the gain in the quality of treatments. The EUD of the OARs was found to be reduced up to 11% and the corresponding NTCP of organs at risk (OARs) was found to be reduced up to 16.5%. These results suggest that, with image guidance by proton radiography, dose to OARs can be reduced and the corresponding NTCPs can be significantly reduced. The study concludes that the proton imaging system can accurately track the motion of the tumor and detect the WEL variations, leading to potential gains in using image-guided proton radiography for lung cancer treatments.

An image-guided precision proton radiation platform for preclinical in vivo research

NASA Astrophysics Data System (ADS)

Ford, E.; Emery, R.; Huff, D.; Narayanan, M.; Schwartz, J.; Cao, N.; Meyer, J.; Rengan, R.; Zeng, J.; Sandison, G.; Laramore, G.; Mayr, N.

2017-01-01

There are many unknowns in the radiobiology of proton beams and other particle beams. We describe the development and testing of an image-guided low-energy proton system optimized for radiobiological research applications. A 50 MeV proton beam from an existing cyclotron was modified to produce collimated beams (as small as 2 mm in diameter). Ionization chamber and radiochromic film measurements were performed and benchmarked with Monte Carlo simulations (TOPAS). The proton beam was aligned with a commercially-available CT image-guided x-ray irradiator device (SARRP, Xstrahl Inc.). To examine the alternative possibility of adapting a clinical proton therapy system, we performed Monte Carlo simulations of a range-shifted 100 MeV clinical beam. The proton beam exhibits a pristine Bragg Peak at a depth of 21 mm in water with a dose rate of 8.4 Gy min-1 (3 mm depth). The energy of the incident beam can be modulated to lower energies while preserving the Bragg peak. The LET was: 2.0 keV µm-1 (water surface), 16 keV µm-1 (Bragg peak), 27 keV µm-1 (10% peak dose). Alignment of the proton beam with the SARRP system isocenter was measured at 0.24 mm agreement. The width of the beam changes very little with depth. Monte Carlo-based calculations of dose using the CT image data set as input demonstrate in vivo use. Monte Carlo simulations of the modulated 100 MeV clinical proton beam show a significantly reduced Bragg peak. We demonstrate the feasibility of a proton beam integrated with a commercial x-ray image-guidance system for preclinical in vivo studies. To our knowledge this is the first description of an experimental image-guided proton beam for preclinical radiobiology research. It will enable in vivo investigations of radiobiological effects in proton beams.

Recent advances in intensity modulated radiotherapy and proton therapy for esophageal cancer.

PubMed

Xi, Mian; Lin, Steven H

2017-07-01

Radiotherapy is an important component of the standard of care for esophageal cancer. In the past decades, significant improvements in the planning and delivery of radiation techniques have led to better dose conformity to the target volume and improved normal tissue sparing. Areas covered: This review focuses on the advances in radiotherapy techniques and summarizes the availably dosimetric and clinical outcomes of intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, proton therapy, and four-dimensional radiotherapy for esophageal cancer, and discusses the challenges and future development of proton therapy. Expert commentary: Although three-dimensional conformal radiotherapy is the standard radiotherapy technique in esophageal cancer, the retrospectively comparative studies strongly suggest that the dosimetric advantage of IMRT over three-dimensional conformal radiotherapy can translate into improved clinical outcomes, despite the lack of prospective randomized evidence. As a novel form of conventional IMRT technique, volumetric modulated arc therapy can produce equivalent or superior dosimetric quality with significantly higher treatment efficiency in esophageal cancer. Compared with photon therapy, proton therapy has the potential to achieve further clinical improvement due to their physical properties; however, prospective clinical data, long-term results, and cost-effectiveness are needed.

A randomized controlled trial of laparoscopic Nissen fundoplication versus proton pump inhibitors for the treatment of patients with chronic gastroesophageal reflux disease (GERD): 3-year outcomes.

PubMed

Anvari, Mehran; Allen, Christopher; Marshall, John; Armstrong, David; Goeree, Ron; Ungar, Wendy; Goldsmith, Charles

2011-08-01

A randomized controlled trial (RCT) investigated patients with gastroesophageal reflux disease (GERD) who were stable and symptomatically controlled with long-term medical therapy to compare ongoing optimized medical therapy with laparoscopic Nissen fundoplication (LNF). Of the 180 patients eligible for randomization, 104 gave informed consent, and 3 withdrew from the study immediately after randomization. The patients randomized to medical therapy received optimized treatment with proton pump inhibitors (PPIs) using a standardized management protocol based on best evidence and published guidelines. The surgical patients underwent LNF by one of four surgeons using a previously published technique. The patients underwent symptom evaluation using the GERD symptom scale (GERSS) and the global visual analog scale (VAS) for overall symptom control. They had 24-h esophageal pH monitoring at baseline and after 3 years. The medical patients were evaluated receiving PPI, and the surgical patients were evaluated not receiving PPI. For the 3-year follow-up assessment, 93 patients were available. At 3 years, surgery was associated with more heartburn-free days, showing a mean difference of -1.35 days per week (p = 0.0077) and a lower VAS score (p = 0.0093) than medical management. Surgical patients reported improved quality of life on the general health subscore of the Medical Outcomes Survey Short Form 36 (SF-36) at 3 years, with a mean difference of -12.19 (p = 0.0124). The groups did not differ significantly in terms of GERSS or acid exposure on 24-h esophageal pH monitoring at 3 years. There were six treatment failures (11.8%) in the surgical group and eight treatment failures (16%) in the medical group by 3 years. For patients whose GERD symptoms are stable and controlled with PPI, continuing medical therapy and laparoscopic antireflux surgery are equally effective, although surgery may result in better symptom control and quality of life.

4D CT-based Treatment Planning for Intensity-Modulated Radiation Therapy and Proton Therapy for Distal Esophagus Cancer

PubMed Central

Zhang, Xiaodong; Zhao, Kuai-Le; Guerrero, Thomas M.; McGuire, Sean E.; Yaremko, Brian; Komaki, Ritsuko; Cox, James D.; Hui, Zhouguang; Li, Yupeng; Newhauser, Wayne D.; Mohan, Radhe; Liao, Zhongxing

2008-01-01

Purpose To compare three-dimensional (3D) and 4D computed tomography (CT)– based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. Materials and Methods IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Results Compared with IMRT, median lung volumes exposed to 5,10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%,5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%,8.4%,5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index CI=1.99) and greater irradiation of the heart (heart-V40=41.8%) compared with the IMRT plan(CI=1.55, heart-V40=35.7%) or the three-beam proton plan (CI=1.46, heart-V40=27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas-filling. Conclusions Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses. PMID:18722278

Four-dimensional computed tomography-based treatment planning for intensity-modulated radiation therapy and proton therapy for distal esophageal cancer.

PubMed

Zhang, Xiaodong; Zhao, Kuai-le; Guerrero, Thomas M; McGuire, Sean E; Yaremko, Brian; Komaki, Ritsuko; Cox, James D; Hui, Zhouguang; Li, Yupeng; Newhauser, Wayne D; Mohan, Radhe; Liao, Zhongxing

2008-09-01

To compare three-dimensional (3D) and four-dimensional (4D) computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. The IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Compared with IMRT, median lung volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index [CI], 1.99) and greater irradiation of the heart (heart-V40, 41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas filling. Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.

SU-E-J-201: Investigation of MRI Guided Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, JS

2015-06-15

Purpose: Image-guided radiation therapy has been employed for cancer treatment to improve the tumor localization accuracy. Radiation therapy with proton beams requires more on this accuracy because the proton beam has larger uncertainty and dramatic dose variation along the beam direction. Among all the image modalities, magnetic-resonance image (MRI) is the best for soft tissue delineation and real time motion monitoring. In this work, we investigated the behavior of the proton beam in magnetic field with Monte Carlo simulations. Methods: A proton Monte Carlo platform, TOPAS, was used for this investigation. Dose calculations were performed with this platform in amore » 30cmx30cmx30cm water phantom for both pencil and broad proton beams with different energies (120, 150 and 180MeV) in different magnetic fields (0.5T, 1T and 3T). The isodose distributions, dose profiles in lateral and beam direction were evaluated. The shifts of the Bragg peak in different magnetic fields for different proton energies were compared and the magnetic field effects on the characters of the dose distribution were analyzed. Results: Significant effects of magnetic field have been observed on the proton beam dose distributions, especially for magnetic field of 1T and up. The effects are more significant for higher energy proton beam because higher energy protons travel longer distance in the magnetic field. The Bragg peak shift in the lateral direction is about 38mm for 180MeV and 11mm for 120MeV proton beams in 3T magnetic field. The peak positions are retracted back for 6mm and 2mm, respectively. The effect on the beam penumbra and dose falloff at the distal edge of the Bragg peak is negligible. Conclusion: Though significant magnetic effects on dose distribution have been observed for proton beams, MRI guided proton therapy is feasible because the magnetic effects on dose is predictable and can be considered in patient dose calculation.« less

Using gEUD based plan analysis method to evaluate proton vs. photon plans for lung cancer radiation therapy.

PubMed

Xiao, Zhiyan; Zou, Wei J; Chen, Ting; Yue, Ning J; Jabbour, Salma K; Parikh, Rahul; Zhang, Miao

2018-03-01

The goal of this study was to exam the efficacy of current DVH based clinical guidelines draw from photon experience for lung cancer radiation therapy on proton therapy. Comparison proton plans and IMRT plans were generated for 10 lung patients treated in our proton facility. A gEUD based plan evaluation method was developed for plan evaluation. This evaluation method used normal lung gEUD(a) curve in which the model parameter "a" was sampled from the literature reported value. For all patients, the proton plans delivered lower normal lung V 5 Gy with similar V 20 Gy and similar target coverage. Based on current clinical guidelines, proton plans were ranked superior to IMRT plans for all 10 patients. However, the proton and IMRT normal lung gEUD(a) curves crossed for 8 patients within the tested range of "a", which means there was a possibility that proton plan would be worse than IMRT plan for lung sparing. A concept of deficiency index (DI) was introduced to quantify the probability of proton plans doing worse than IMRT plans. By applying threshold on DI, four patients' proton plan was ranked inferior to the IMRT plan. Meanwhile if a threshold to the location of curve crossing was applied, 6 patients' proton plan was ranked inferior to the IMRT plan. The contradictory ranking results between the current clinical guidelines and the gEUD(a) curve analysis demonstrated there is potential pitfalls by applying photon experience directly to the proton world. A comprehensive plan evaluation based on radio-biological models should be carried out to decide if a lung patient would really be benefit from proton therapy. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

An analytical reconstruction model of the spread-out Bragg peak using laser-accelerated proton beams.

PubMed

Tao, Li; Zhu, Kun; Zhu, Jungao; Xu, Xiaohan; Lin, Chen; Ma, Wenjun; Lu, Haiyang; Zhao, Yanying; Lu, Yuanrong; Chen, Jia-Er; Yan, Xueqing

2017-07-07

With the development of laser technology, laser-driven proton acceleration provides a new method for proton tumor therapy. However, it has not been applied in practice because of the wide and decreasing energy spectrum of laser-accelerated proton beams. In this paper, we propose an analytical model to reconstruct the spread-out Bragg peak (SOBP) using laser-accelerated proton beams. Firstly, we present a modified weighting formula for protons of different energies. Secondly, a theoretical model for the reconstruction of SOBPs with laser-accelerated proton beams has been built. It can quickly calculate the number of laser shots needed for each energy interval of the laser-accelerated protons. Finally, we show the 2D reconstruction results of SOBPs for laser-accelerated proton beams and the ideal situation. The final results show that our analytical model can give an SOBP reconstruction scheme that can be used for actual tumor therapy.

Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer.

PubMed

Chang, Joe Y; Komaki, Ritsuko; Lu, Charles; Wen, Hong Y; Allen, Pamela K; Tsao, Anne; Gillin, Michael; Mohan, Radhe; Cox, James D

2011-10-15

The authors sought to improve the toxicity of conventional concurrent chemoradiation therapy for stage III nonsmall cell lung cancer (NSCLC) by using proton-beam therapy to escalate the radiation dose to the tumor. They report early results of a phase 2 study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival. Forty-four patients with stage III NSCLC were treated with 74 grays (radiobiologic equivalent) proton therapy with weekly carboplatin (area under the curve, 2 U) and paclitaxel (50 mg/m(2)). Disease was staged with positron emission tomography/computed tomography (CT), and treatments were simulated with 4-dimensional (4D) CT to account for tumor motion. Protons were delivered as passively scattered beams, and treatment simulation was repeated during the treatment process to determine the need for adaptive replanning. Median follow-up time was 19.7 months (range, 6.1-44.4 months), and median overall survival time was 29.4 months. No patient experienced grade 4 or 5 proton-related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n = 5), esophagitis (n = 5), and pneumonitis (n = 1). Nine (20.5%) patients experienced local disease recurrence, but only 4 (9.1%) had isolated local failure. Four (9.1%) patients had regional lymph node recurrence, but only 1 (2.3%) had isolated regional recurrence. Nineteen (43.2%) patients developed distant metastasis. The overall survival and progression-free survival rates were 86% and 63% at 1 year. Concurrent high-dose proton therapy and chemotherapy are well tolerated, and the median survival time of 29.4 months is encouraging for unresectable stage III NSCLC. Copyright © 2011 American Cancer Society.

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a monte carlo study.

PubMed

Jung, Joo-Young; Yoon, Do-Kun; Barraclough, Brendan; Lee, Heui Chang; Suh, Tae Suk; Lu, Bo

2017-06-13

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy.

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a Monte Carlo study

PubMed Central

Barraclough, Brendan; Lee, Heui Chang; Suh, Tae Suk; Lu, Bo

2017-01-01

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy. PMID:28427153

Status of the Proton Therapy Project at IUCF and the Midwest Proton Radiotherapy Institute

NASA Astrophysics Data System (ADS)

Klein, Susan B.

2003-08-01

The first proton therapy patient was successfully treated for astrocytoma using a modified nuclear experimentation beam line and in-house treatment planning in 1993. In 1998, IUCF constructed an eye treatment clinic, and conducted a phase III clinical trial investigating proton radiation treatment of AMD. Treatment was planned using Eyeplan modified to match the IUCF beam characteristics. MPRI was conceptualized in 1996 by a consortium of physicians and physicists. Reconfiguration began in 2000; construction of the achromatic trunk line began in 2001, followed by manufacture of 4 energy selection lines and two fixed horizontal beam treatment lines. Two isocentric, rotational gantries will be installed following completion of the horizontal beam lines. A fifth line will supply the full-time radiation effects research station. Standard proton delivery out of the main stage is specified at 500 nA of 205 MeV. Clinic construction began in April, 2002 and will be completed by mid-December. Design, construction and operation of these proton facilities have been accomplished by the proton therapy group at IUCF.

Hadron therapy: history, status, prospects

NASA Astrophysics Data System (ADS)

Klenov, G. I.; Khoroshkov, V. S.

2016-08-01

A brief historical review is given of external radiation therapy (RT), one of the main cancer treatment methods along with surgery and chemotherapy. Cellular mechanisms of radiation damage are described. Special attention is paid to hadron (proton and ion) therapy, its history, results, problems, challenges, current trends, and prospects. Undeniably great contributions to proton therapy have been made by Russian researchers, notably at the experimental centers that have operated since the mid-20th century at the Joint Institute for Nuclear Research, the A I Alikhanov Institute for Theoretical and Experimental Physics (ITEP), and the B P Konstantinov Petersburg Institute of Nuclear Physics. A quarter of the global clinical experience was accumulated by 1990 at the world's largest ITEP-hosted multicabin proton therapy center.

Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

NASA Astrophysics Data System (ADS)

Poludniowski, G.; Allinson, N. M.; Anaxagoras, T.; Esposito, M.; Green, S.; Manolopoulos, S.; Nieto-Camero, J.; Parker, D. J.; Price, T.; Evans, P. M.

2014-06-01

Despite the early recognition of the potential of proton imaging to assist proton therapy (Cormack 1963 J. Appl. Phys. 34 2722), the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as computed tomography (CT), the water-equivalent-path-length that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS active pixel sensor technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed.

Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

PubMed Central

Poludniowski, G; Allinson, N M; Anaxagoras, T; Esposito, M; Green, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Price, T; Evans, P M

2014-01-01

Despite the early recognition of the potential of proton imaging to assist proton therapy the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as Computed Tomography (CT), the Water-Equivalent-Path-Length (WEPL) that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS Active Pixel Sensor (APS) technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed. PMID:24785680

How Does Proton Radiation Therapy Work?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lincoln, Don

A cancer diagnosis can be a devastating thing to hear, but new treatments are greatly improving a person’s chance of being cured. In this video, Fermilab’s Dr. Don Lincoln explains the physics of an exciting treatment option, called proton radiation therapy, which is far superior to traditional therapy, at least in some cases.

Proton Radiotherapy for Pediatric Central Nervous System Germ Cell Tumors: Early Clinical Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, Shannon M., E-mail: smacdonald@partners.or; Trofimov, Alexei; Safai, Sairos

Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost. Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case. Results: Twenty-two patients were treatedmore » with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes. Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment.« less

SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pham, R; Sun, B; Zhao, T

Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculatedmore » on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.« less

Development of proton computed tomography detectors for applications in hadron therapy

NASA Astrophysics Data System (ADS)

Bashkirov, Vladimir A.; Johnson, Robert P.; Sadrozinski, Hartmut F.-W.; Schulte, Reinhard W.

2016-02-01

Radiation therapy with protons and heavier ions is an attractive form of cancer treatment that could enhance local control and survival of cancers that are currently difficult to cure and lead to less side effects due to sparing of normal tissues. However, particle therapy faces a significant technical challenge because one cannot accurately predict the particle range in the patient using data provided by existing imaging technologies. Proton computed tomography (pCT) is an emerging imaging modality capable of improving the accuracy of range prediction. In this paper, we describe the successive pCT scanners designed and built by our group with the goal to support particle therapy treatment planning and image guidance by reconstructing an accurate 3D map of the stopping power relative to water in patient tissues. The pCT scanners we have built to date consist of silicon telescopes, which track the proton before and after the object to be reconstructed, and an energy or range detector, which measures the residual energy and/or range of the protons used to evaluate the water equivalent path length (WEPL) of each proton in the object. An overview of a decade-long evolution of the conceptual design of pCT scanners and their calibration is given. Results of scanner performance tests are presented, which demonstrate that the latest pCT scanner approaches readiness for clinical applications in hadron therapy.

SU-E-T-124: Dosimetric Comparison of HDR Brachytherapy and Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, J; Wu, H; Das, I

2014-06-01

Purpose: Brachytherapy is known to be able to deliver more radiation dose to tumor while minimizing radiation dose to surrounding normal tissues. Proton therapy also provides superior dose distribution due to Bragg peak. Since both HDR and Intensity Modulated Proton Therapy (IMPT) are beneficial for their quick dose drop off, our goal in this study is to compare the pace of dose gradient drop-off between HDR and IMPT plans based on the same CT image data-set. In addition, normal tissues sparing were also compared among HDR, IMPT and SBRT. Methods: Five cervical cancer cases treated with EBRT + HDR boostmore » combination with Tandem and Ovoid applicator were used for comparison purpose. Original HDR plans with prescribed dose of 5.5 Gy x 5 fractions were generated and optimized. The 100% isodose line of HDR plans was converted to a dose volume, and treated as CTV for IMPT and SBRT planning. The same HDR CT scans were also used for IMPT plan and SBRT plan for direct comparison. The philosophy of the IMPT and SBRT planning was to create the same CTV coverage as HDR plans. All three modalities treatment plans were compared to each other with a set of predetermined criteria. Results: With similar target volume coverage in cervix cancer boost treatment, HDR provides a slightly sharper dose drop-off from 100% to 50% isodose line, averagely in all directions compared to IMPT. However, IMPT demonstrated more dose gradient drop-off at the junction of the target and normal tissues by providing more normal tissue sparing and superior capability to reduce integral dose. Conclusion: IMPT is capable of providing comparable dose drop-off as HDR. IMPT can be explored as replacement for HDR brachytherapy in various applications.« less

SU-F-T-140: Assessment of the Proton Boron Fusion Reaction for Practical Radiation Therapy Applications Using MCNP6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adam, D; Bednarz, B

Purpose: The proton boron fusion reaction is a reaction that describes the creation of three alpha particles as the result of the interaction of a proton incident upon a 11B target. Theoretically, the proton boron fusion reaction is a desirable reaction for radiation therapy applications in that, with the appropriate boron delivery agent, it could potentially combine the localized dose delivery protons exhibit (Bragg peak) and the local deposition of high LET alpha particles in cancerous sites. Previous efforts have shown significant dose enhancement using the proton boron fusion reaction; the overarching purpose of this work is an attempt tomore » validate previous Monte Carlo results of the proton boron fusion reaction. Methods: The proton boron fusion reaction, 11B(p, 3α), is investigated using MCNP6 to assess the viability for potential use in radiation therapy. Simple simulations of a proton pencil beam incident upon both a water phantom and a water phantom with an axial region containing 100ppm boron were modeled using MCNP6 in order to determine the extent of the impact boron had upon the calculated energy deposition. Results: The maximum dose increase calculated was 0.026% for the incident 250 MeV proton beam scenario. The MCNP simulations performed demonstrated that the proton boron fusion reaction rate at clinically relevant boron concentrations was too small in order to have any measurable impact on the absorbed dose. Conclusion: For all MCNP6 simulations conducted, the increase of absorbed dose of a simple water phantom due to the 11B(p, 3α) reaction was found to be inconsequential. In addition, it was determined that there are no good evaluations of the 11B(p, 3α) reaction for use in MCNPX/6 and further work should be conducted in cross section evaluations in order to definitively evaluate the feasibility of the proton boron fusion reaction for use in radiation therapy applications.« less

Clinical equipoise: Protons and the child with craniopharyngioma.

PubMed

Conroy, Ruth; Gomes, Lavier; Owen, Catherine; Buchsbaum, Jeffrey; Ahern, Verity

2015-06-01

Childhood craniopharyngioma is a complex condition to manage. Survival figures are high but the potential for long-term morbidity is great. There is much debate regarding the best management for these tumours with increasing interest in the use of proton beam therapy. We have therefore reviewed our radiotherapy (RT) practice at Westmead Hospital and the literature regarding the use of protons for these children. Three children have received fractionated stereotactic RT for craniopharyngioma at Westmead Hospital since 2007. Each RT plan was reviewed and additional organs at risk were contoured to enable comparison with published proton data. Planning target volume coverage was similar with all modalities: with the conformity index ranging from 0.70 to 0.78 in our patients compared with 0.50-0.84 in the published data. RT dose to temporal lobes, hippocampi and whole brain was also similar with protons and photons. Proton beam therapy may give lower dose to the Circle of Willis than stereotactic RT. Currently there is no clear evidence that proton beam therapy will improve survival or reduce morbidity for children with craniopharyngioma. However, proton therapy has the potential to reduce RT dose to the Circle of Willis, which may reduce the risk of future cerebrovascular complications. We propose that more resources should be allocated to ensuring these patients are managed by experienced multidisciplinary teams through the continuum from diagnosis to long-term follow-up. © 2014 The Royal Australian and New Zealand College of Radiologists.

Optimizing a three-stage Compton camera for measuring prompt gamma rays emitted during proton radiotherapy

PubMed Central

Peterson, S W; Robertson, D; Polf, J

2011-01-01

In this work, we investigate the use of a three-stage Compton camera to measure secondary prompt gamma rays emitted from patients treated with proton beam radiotherapy. The purpose of this study was (1) to develop an optimal three-stage Compton camera specifically designed to measure prompt gamma rays emitted from tissue and (2) to determine the feasibility of using this optimized Compton camera design to measure and image prompt gamma rays emitted during proton beam irradiation. The three-stage Compton camera was modeled in Geant4 as three high-purity germanium detector stages arranged in parallel-plane geometry. Initially, an isotropic gamma source ranging from 0 to 15 MeV was used to determine lateral width and thickness of the detector stages that provided the optimal detection efficiency. Then, the gamma source was replaced by a proton beam irradiating a tissue phantom to calculate the overall efficiency of the optimized camera for detecting emitted prompt gammas. The overall calculated efficiencies varied from ~10−6 to 10−3 prompt gammas detected per proton incident on the tissue phantom for several variations of the optimal camera design studied. Based on the overall efficiency results, we believe it feasible that a three-stage Compton camera could detect a sufficient number of prompt gammas to allow measurement and imaging of prompt gamma emission during proton radiotherapy. PMID:21048295

Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amsbaugh, Mark J.; Grosshans, David R., E-mail: dgrossha@mdanderson.org; McAleer, Mary Frances

2012-08-01

Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas,more » and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.« less

Intelligent ePR system for evidence-based research in radiotherapy: proton therapy for prostate cancer.

PubMed

Le, Anh H; Liu, Brent; Schulte, Reinhard; Huang, H K

2011-11-01

Proton therapy (PT) utilizes high energy particle proton beam to kill cancer cells at the target region for target cancer therapy. Due to the physical properties of the proton beam, PT delivers dose with higher precision and no exit dose compared to conventional radiotherapy. In PT, patient data are distributed among multiple systems, a hindrance to research on efficacy and effectiveness. A data mining method and a treatment plan navigator utilizing the infrastructure and data repository of a PT electronic patient record (ePR) was developed to minimize radiation toxicity and improve outcomes in prostate cancer treatment. MATERIALS/METHOD(S): The workflow of a proton therapy treatment in a radiation oncology department was reviewed, and a clinical data model and data flow were designed. A prototype PT ePR system with DICOM compliance was developed to manage prostate cancer patient images, treatment plans, and related clinical data. The ePR system consists of four main components: (1) Data Gateway; (2) ePR Server; (3) Decision Support Tools; and (4) Visualization and Display Tools. Decision support and visualization tools are currently developed based on DICOM images, DICOM-RT and DICOM-RT-ION objects data from prostate cancer patients treated with hypofractionation protocol proton therapy were used for evaluating ePR system effectiveness. Each patient data set includes a set of computed tomography (CT) DICOM images and four DICOM-RT and RT-ION objects. In addition, clinical outcomes data collected from PT cases were included to establish a knowledge base for outcomes analysis. A data mining search engine and an intelligent treatment plan navigator (ITPN) were developed and integrated with the ePR system. Evaluation was based on a data set of 39 PT patients and a hypothetical patient. The ePR system was able to facilitate the proton therapy workflow. The PT ePR system was feasible for prostate cancer patient treated with hypofractionation protocol in proton therapy. This ePR system improves efficiency in data collection and integration to facilitate outcomes analysis.

Implementation and verification of nuclear interactions in a Monte-Carlo code for the Procom-ProGam proton therapy planning system

NASA Astrophysics Data System (ADS)

Kostyuchenko, V. I.; Makarova, A. S.; Ryazantsev, O. B.; Samarin, S. I.; Uglov, A. S.

2014-06-01

A great breakthrough in proton therapy has happened in the new century: several tens of dedicated centers are now operated throughout the world and their number increases every year. An important component of proton therapy is a treatment planning system. To make calculations faster, these systems usually use analytical methods whose reliability and accuracy do not allow the advantages of this method of treatment to implement to the full extent. Predictions by the Monte Carlo (MC) method are a "gold" standard for the verification of calculations with these systems. At the Institute of Experimental and Theoretical Physics (ITEP) which is one of the eldest proton therapy centers in the world, an MC code is an integral part of their treatment planning system. This code which is called IThMC was developed by scientists from RFNC-VNIITF (Snezhinsk) under ISTC Project 3563.

[Proton beam therapy].

PubMed

Ogino, Takashi

2006-04-01

Proton beam therapy (PBT) has made it possible to deliver a higher concentration of radiation to the tumor by its Bragg-peak, and is easy to utilize due to the fact that its biological characteristics are identical with X-rays. PBT has a half-century history, and more than 40,000 patients have been reported as having had treatments with proton beams worldwide. The historic change to this therapy occurred in the 1990s, when the Loma Linda University Medical Center began its clinical activity as the first hospital in the world to utilize a medically dedicated proton therapy facility. Since then, similar hospital-based medically dedicated facilities have been constructed. Results from around the world have shown the therapeutic superiority of PBT over alternative treatment options for ocular melanoma, skull base sarcoma, head & neck cancer, lung cancer,esophageal cancer, hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve further advancement both clinically and technologically.

Helical Tomotherapy vs. Intensity-Modulated Proton Therapy for Whole Pelvis Irradiation in High-Risk Prostate Cancer Patients: Dosimetric, Normal Tissue Complication Probability, and Generalized Equivalent Uniform Dose Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widesott, Lamberto, E-mail: widesott@yahoo.it; Pierelli, Alessio; Fiorino, Claudio

2011-08-01

Purpose: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for high-risk prostate cancer (HRPCa) patients. Methods and Materials: The plans of 8 patients with HRPCa treated with HT were compared with IMPT plans with two quasilateral fields set up (-100{sup o}; 100{sup o}) and optimized with the Hyperion treatment planning system. Both techniques were optimized to simultaneously deliver 74.2 Gy/Gy relative biologic effectiveness (RBE) in 28 fractions on planning target volumes (PTVs)3-4 (P + proximal seminal vesicles), 65.5 Gy/Gy(RBE) on PTV2 (distal seminal vesicles and rectum/prostate overlapping), and 51.8 Gy/Gy(RBE) to PTV1 (pelvic lymph nodes). Normalmore » tissue calculation probability (NTCP) calculations were performed for the rectum, and generalized equivalent uniform dose (gEUD) was estimated for the bowel cavity, penile bulb and bladder. Results: A slightly better PTV coverage and homogeneity of target dose distribution with IMPT was found: the percentage of PTV volume receiving {>=}95% of the prescribed dose (V{sub 95%}) was on average >97% in HT and >99% in IMPT. The conformity indexes were significantly lower for protons than for photons, and there was a statistically significant reduction of the IMPT dosimetric parameters, up to 50 Gy/Gy(RBE) for the rectum and bowel and 60 Gy/Gy(RBE) for the bladder. The NTCP values for the rectum were higher in HT for all the sets of parameters, but the gain was small and in only a few cases statistically significant. Conclusions: Comparable PTV coverage was observed. Based on NTCP calculation, IMPT is expected to allow a small reduction in rectal toxicity, and a significant dosimetric gain with IMPT, both in medium-dose and in low-dose range in all OARs, was observed.« less

Accelerator driven neutron source design via beryllium target and 208Pb moderator for boron neutron capture therapy in alternative treatment strategy by Monte Carlo method.

PubMed

Khorshidi, Abdollah

2017-01-01

The reactor has increased its area of application into medicine especially boron neutron capture therapy (BNCT); however, accelerator-driven neutron sources can be used for therapy purposes. The present study aimed to discuss an alternative method in BNCT functions by a small cyclotron with low current protons based on Karaj cyclotron in Iran. An epithermal neutron spectrum generator was simulated with 30 MeV proton energy for BNCT purposes. A low current of 300 μA of the proton beam in spallation target concept via 9Be target was accomplished to model neutron spectrum using 208Pb moderator around the target. The graphite reflector and dual layer collimator were planned to prevent and collimate the neutrons produced from proton interactions. Neutron yield per proton, energy distribution, flux, and dose components in the simulated head phantom were estimated by MCNPX code. The neutron beam quality was investigated by diverse filters thicknesses. The maximum epithermal flux transpired using Fluental, Fe, Li, and Bi filters with thicknesses of 7.4, 3, 0.5, and 4 cm, respectively; as well as the epithermal to thermal neutron flux ratio was 161. Results demonstrated that the induced neutrons from a low energy and low current proton may be effective in tumor therapy using 208Pb moderator with average lethargy and also graphite reflector with low absorption cross section to keep the generated neutrons. Combination of spallation-based BNCT and proton therapy can be especially effective, if a high beam intensity cyclotron becomes available.

Electronic stopping power calculation for water under the Lindhard formalism for application in proton computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerrero, A. F., E-mail: afguerreror@uqvirtual.edu.co; Mesa, J., E-mail: jmesa@ibb.unesp.br

2016-07-07

Because of the behavior that charged particles have when they interact with biological material, proton therapy is shaping the future of radiation therapy in cancer treatment. The planning of radiation therapy is made up of several stages. The first one is the diagnostic image, in which you have an idea of the density, size and type of tumor being treated; to understand this it is important to know how the particles beam interacts with the tissue. In this work, by using de Lindhard formalism and the Y.R. Waghmare model for the charge distribution of the proton, the electronic stopping powermore » (SP) for a proton beam interacting with a liquid water target in the range of proton energies 10{sup 1} eV - 10{sup 10} eV taking into account all the charge states is calculated.« less

Water-soluble core/shell nanoparticles for proton therapy through particle-induced radiation

NASA Astrophysics Data System (ADS)

Park, Jeong Chan; Jung, Myung-Hwan; Kim, Maeng Jun; Kim, Kye-Ryung

2015-02-01

Metallic nanoparticles have been used in biomedical applications such as magnetic resonance imaging (MRI), therapy, and drug delivery systems. Metallic nanoparticles as therapeutic tools have been demonstrated using radio-frequency magnetic fields or near-infrared light. Recently, therapeutic applications of metallic nanomaterials combined with proton beams have been reported. Particle-induced radiation from metallic nanoparticles, which can enhance the therapeutic effects of proton therapy, was released when the nanoparticles were bombarded by a high-energy proton beam. Core/shell nanoparticles, especially Au-coated magnetic nanoparticles, have drawn attention in biological applications due to their attractive characteristics. However, studies on the phase transfer of organic-ligand-based core/shell nanoparticles into water are limited. Herein, we demonstrated that hydrophobic core/shell structured nanomaterials could be successfully dispersed in water through chloroform/surfactant mixtures. The effects of the core/shell nanomaterials and the proton irradiation on Escherichia coli (E. coli) were also explored.

A comparison of intensity modulated x-ray therapy to intensity modulated proton therapy for the delivery of non-uniform dose distributions

NASA Astrophysics Data System (ADS)

Flynn, Ryan

2007-12-01

The distribution of biological characteristics such as clonogen density, proliferation, and hypoxia throughout tumors is generally non-uniform, therefore it follows that the optimal dose prescriptions should also be non-uniform and tumor-specific. Advances in intensity modulated x-ray therapy (IMXT) technology have made the delivery of custom-made non-uniform dose distributions possible in practice. Intensity modulated proton therapy (IMPT) has the potential to deliver non-uniform dose distributions as well, while significantly reducing normal tissue and organ at risk dose relative to IMXT. In this work, a specialized treatment planning system was developed for the purpose of optimizing and comparing biologically based IMXT and IMPT plans. The IMXT systems of step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) and the IMPT systems of intensity modulated spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT), were simulated. A thorough phantom study was conducted in which several subvolumes, which were contained within a base tumor region, were boosted or avoided with IMXT and IMPT. Different boosting situations were simulated by varying the size, proximity, and the doses prescribed to the subvolumes, and the size of the phantom. IMXT and IMPT were also compared for a whole brain radiation therapy (WBRT) case, in which a brain metastasis was simultaneously boosted and the hippocampus was avoided. Finally, IMXT and IMPT dose distributions were compared for the case of non-uniform dose prescription in a head and neck cancer patient that was based on PET imaging with the Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) hypoxia marker. The non-uniform dose distributions within the tumor region were comparable for IMXT and IMPT. IMPT, however, was capable of delivering the same non-uniform dose distributions within a tumor using a 180° arc as for a full 360° rotation, which resulted in the reduction of normal tissue integral dose by a factor of up to three relative to IMXT, and the complete sparing of organs at risk distal to the tumor region.

Effect of proton pump inhibitors on markers of risk for high-grade dysplasia and oesophageal cancer in Barrett's oesophagus.

PubMed

Hillman, L C; Chiragakis, L; Shadbolt, B; Kaye, G L; Clarke, A C

2008-02-15

It has been shown that the presence on diagnosis of endoscopic macroscopic markers indicates a high-risk group for Barrett's oesophagus. To determine whether proton pump inhibitor therapy prior to diagnosis of Barrett's oesophagus influences markers for risk development of subsequent high-grade dysplasia/adenocarcinoma. A review of all patients with Barrett's oesophagus entering a surveillance programme was undertaken. Five hundred and two patients diagnosed with Barrett's oesophagus were assessed on diagnosis for endoscopic macroscopic markers or low-grade dysplasia. Subsequent development of high-grade dysplasia/adenocarcinoma was documented. The relationship between the initiation of proton pump inhibitor therapy prior to the diagnosis of BE and the presence of macroscopic markers or low-grade dysplasia at entry was determined. Fourteen patients developed high-grade dysplasia/adenocarcinoma during surveillance. Patients who entered without prior proton pump inhibitor therapy were 3.4 times (95% CI: 1.98-5.85) more likely to have a macroscopic marker or low-grade dysplasia than those patients already on a proton pump inhibitor. Use of proton pump inhibitor therapy prior to diagnosis of Barrett's oesophagus significantly reduced the presence of markers used to stratify patient risk. Widespread use of proton pump inhibitors will confound surveillance strategies for patients with Barrett's oesophagus based on entry characteristics but is justified because of the lower risk of neoplastic progression.

High density scintillating glass proton imaging detector

NASA Astrophysics Data System (ADS)

Wilkinson, C. J.; Goranson, K.; Turney, A.; Xie, Q.; Tillman, I. J.; Thune, Z. L.; Dong, A.; Pritchett, D.; McInally, W.; Potter, A.; Wang, D.; Akgun, U.

2017-03-01

In recent years, proton therapy has achieved remarkable precision in delivering doses to cancerous cells while avoiding healthy tissue. However, in order to utilize this high precision treatment, greater accuracy in patient positioning is needed. An accepted approximate uncertainty of +/-3% exists in the current practice of proton therapy due to conversions between x-ray and proton stopping power. The use of protons in imaging would eliminate this source of error and lessen the radiation exposure of the patient. To this end, this study focuses on developing a novel proton-imaging detector built with high-density glass scintillator. The model described herein contains a compact homogeneous proton calorimeter composed of scintillating, high density glass as the active medium. The unique geometry of this detector allows for the measurement of both the position and residual energy of protons, eliminating the need for a separate set of position trackers in the system. Average position and energy of a pencil beam of 106 protons is used to reconstruct the image rather than by analyzing individual proton data. Simplicity and efficiency were major objectives in this model in order to present an imaging technique that is compact, cost-effective, and precise, as well as practical for a clinical setting with pencil-beam scanning proton therapy equipment. In this work, the development of novel high-density glass scintillator and the unique conceptual design of the imager are discussed; a proof-of-principle Monte Carlo simulation study is performed; preliminary two-dimensional images reconstructed from the Geant4 simulation are presented.

Proton therapy versus intensity modulated x-ray therapy in the treatment of prostate cancer: Estimating secondary cancer risks

NASA Astrophysics Data System (ADS)

Fontenot, Jonas David

External beam radiation therapy is used to treat nearly half of the more than 200,000 new cases of prostate cancer diagnosed in the United States each year. During a radiation therapy treatment, healthy tissues in the path of the therapeutic beam are exposed to high doses. In addition, the whole body is exposed to a low-dose bath of unwanted scatter radiation from the pelvis and leakage radiation from the treatment unit. As a result, survivors of radiation therapy for prostate cancer face an elevated risk of developing a radiogenic second cancer. Recently, proton therapy has been shown to reduce the dose delivered by the therapeutic beam to normal tissues during treatment compared to intensity modulated x-ray therapy (IMXT, the current standard of care). However, the magnitude of stray radiation doses from proton therapy, and their impact on this incidence of radiogenic second cancers, was not known. The risk of a radiogenic second cancer following proton therapy for prostate cancer relative to IMXT was determined for 3 patients of large, median, and small anatomical stature. Doses delivered to healthy tissues from the therapeutic beam were obtained from treatment planning system calculations. Stray doses from IMXT were taken from the literature, while stray doses from proton therapy were simulated using a Monte Carlo model of a passive scattering treatment unit and an anthropomorphic phantom. Baseline risk models were taken from the Biological Effects of Ionizing Radiation VII report. A sensitivity analysis was conducted to characterize the uncertainty of risk calculations to uncertainties in the risk model, the relative biological effectiveness (RBE) of neutrons for carcinogenesis, and inter-patient anatomical variations. The risk projections revealed that proton therapy carries a lower risk for radiogenic second cancer incidence following prostate irradiation compared to IMXT. The sensitivity analysis revealed that the results of the risk analysis depended only weakly on uncertainties in the risk model and inter-patient variations. Second cancer risks were sensitive to changes in the RBE of neutrons. However, the findings of the study were qualitatively consistent for all patient sizes and risk models considered, and for all neutron RBE values less than 100.

Characterization of Relative Biological Effectiveness for Proton Therapy in Human Cancer Cell Lines

NASA Astrophysics Data System (ADS)

Howard, Michelle Erin

Purpose: Relative biological effectiveness (RBE) is utilized to account for the differences in biological effect from different radiation types. The RBE for proton therapy remains uncertain as it has been shown to vary from the clinically used value of 1.1. The purpose of this thesis was to investigate the RBE of protons as compared to X-rays and correlate the biological differences with the underlying physics. Methods: Three cell lines were irradiated (CHO, Chinese hamster ovary; A549, human lung adenocarcinoma; and T98, human glioma) and assessed for cell survival using clonogenic assay. Cells were irradiated with 71 and 160 MeV protons at depths along the Bragg curve and 6 MV X-rays to various doses. To correlate the underlying physics to RBE, both the dose averaged lineal energy (y¯D) and dose averaged LET (LETd) investigated. The microdosimetric quantity y¯D was measured under similar conditions as the cells using a solid state microdosimeter and LETd calculated using Monte Carlo (MC) simulations. Survival data were fit using the linear quadratic model. RBE values were calculated by comparing the physical dose (D6MV/Dp) that results in 50% (RBE0.5), 10% (RBE0.1) cell survival, and survival after 2Gy (RBE2 Gy).. Results: For 10% and 50% survival, the RBE for all three cell lines increased with decreasing proton energy (or increased depth). The RBE at 2Gy also increased with a decrease in proton energy in all cases, within experimental error. Results also showed the experimental end point proved to influence the measured proton RBE as well with larger values corresponding to 50% cell survival. Cell type had the least influence on proton RBE compared to proton energy and end point. Results from this study showed an increase in RBE corresponded to an increase in both LETd and y¯ D. Additionally, the measured y¯D and calculated LET d values did not match for all the points of measurement along the curve for the 71 and 160 MeV proton beams. Conclusion: Proton RBE depends on proton energy, cell type and LET. Cellular response to radiation is varied and can be seen in the data from CHO, A549 and T98 cell lines irradiated with 71 MeV protons. Both A549 and T98 cells generally had higher RBE values, indicating a greater biological response to protons. The RBE values in this study vary from 0.89- 2.40, indicating the clinical value of 1.1 may not be suitable in all cases. Innovation/impact: The rare but devastating complication of brainstem necrosis has occurred recently in pediatric patients treated with proton therapy (PT). Many believe these effects are due to the uncertainty in the RBE of PT, which may be underestimating the biological dose near critical structures. An increased confidence in RBE for PT can lead to a decrease in toxicity to normal tissues and therefore a decrease in secondary or recurrent cancer and better overall patient outcomes. This study is one of the first to consider the intricacies of proton RBE dependence on parameters such as cell type, proton energy and LET. The broader implications of understanding RBE variations in a cell-specific manner will allow for biologically optimized treatment planning and an overall decrease in PT uncertainty which may lead to improved patient outcomes. Further, this was the first study, to our knowledge, to measure y¯D with a solid state detector for the comparison with measured RBE values.

SU-E-T-621: Planning Methodologies for Cancer of the Anal Canal: Comparing IMRT, Rapid Arc, and Pencil Beam Scanning Proton Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGlade, J; Kassaee, A

2015-06-15

Purpose: To evaluate planning methods for anal canal cancer and compare the results of 9-field Intensity Modulated Radiotherapy (IMRT), Volumetric Modulated Arc Therapy (Varian, RapidArc), and Proton Pencil Beam Scanning (PBS). Methods: We generated plans with IMRT, RapidArc (RA) and PBS for twenty patients for both initial phase including nodes and cone down phase of treatment using Eclipe (Varian). We evaluated the advantage of each technique for each phase. RA plans used 2 to 4 arcs and various collimator orientations. PBS used two posterior oblique fields. We evaluated the plans comparing dose volume histogram (DVH), locations of hot spots, andmore » PTV dose conformity. Results: Due to complex shape of target, for RA plans, multiple arcs (>2) are required to achieve optimal PTV conformity. When the PTV exceeds 15 cm in the superior-inferior direction, limitations of deliverability start to dominate. The PTV should be divided into a superior and an inferior structure. The optimization is performed with fixed jaws for each structure and collimator set to 90 degrees for the inferior PTV. Proton PBS plans show little advantage in small bowel sparing when treating the nodes. However, PBS plan reduces volumetric dose to the bladder at the cost of higher doses to the perineal skin. IMRT plans provide good target conformity, but they generate hot spots outside of the target volume. Conclusion: When using one planning technique for entire course of treatment, Multiple arc (>2) RA plans are better as compared to IMRT and PBS plans. When combining techniques, RA for the initial phase in combination with PBS for the cone down phase results in the most optimal plans.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Botas, Pablo; Faculty of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg

Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dosemore » objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.« less

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced non-small cell lung cancer.

PubMed

Wu, Chen-Ta; Motegi, Atsushi; Motegi, Kana; Hotta, Kenji; Kohno, Ryosuke; Tachibana, Hidenobu; Kumagai, Motoki; Nakamura, Naoki; Hojo, Hidehiro; Niho, Seiji; Goto, Koichi; Akimoto, Tetsuo

2016-08-10

To assess the feasibility of proton beam therapy for the patients with locally advanced non-small lung cancer. The dosimetry was analyzed retrospectively to calculate the doses to organs at risk, such as the lung, heart, esophagus and spinal cord. A dosimetric comparison between proton beam therapy and dummy photon radiotherapy (three-dimensional conformal radiotherapy) plans was performed. Dummy intensity-modulated radiotherapy plans were also generated for the patients for whom curative three-dimensional conformal radiotherapy plans could not be generated. Overall, 33 patients with stage III non-small cell lung cancer were treated with proton beam therapy between December 2011 and August 2014. The median age of the eligible patients was 67 years (range: 44-87 years). All the patients were treated with chemotherapy consisting of cisplatin/vinorelbine or carboplatin. The median prescribed dose was 60 GyE (range: 60-66 GyE). The mean normal lung V20 GyE was 23.6% (range: 14.9-32%), and the mean normal lung dose was 11.9 GyE (range: 6.0-19 GyE). The mean esophageal V50 GyE was 25.5% (range: 0.01-63.6%), the mean heart V40 GyE was 13.4% (range: 1.4-29.3%) and the mean maximum spinal cord dose was 40.7 GyE (range: 22.9-48 GyE). Based on dummy three-dimensional conformal radiotherapy planning, 12 patients were regarded as not being suitable for radical thoracic three-dimensional conformal radiotherapy. All the dose parameters of proton beam therapy, except for the esophageal dose, were lower than those for the dummy three-dimensional conformal radiotherapy plans. In comparison to the intensity-modulated radiotherapy plan, proton beam therapy also achieved dose reduction in the normal lung. None of the patients experienced grade 4 or worse non-hematological toxicities. Proton beam therapy for patients with stage III non-small cell lung cancer was feasible and was superior to three-dimensional conformal radiotherapy for several dosimetric parameters. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SU-E-T-574: Novel Chance-Constrained Optimization in Intensity-Modulated Proton Therapy Planning to Account for Range and Patient Setup Uncertainties

DOE Office of Scientific and Technical Information (OSTI.GOV)

An, Y; Liang, J; Liu, W

2015-06-15

Purpose: We propose to apply a probabilistic framework, namely chanceconstrained optimization, in the intensity-modulated proton therapy (IMPT) planning subject to range and patient setup uncertainties. The purpose is to hedge against the influence of uncertainties and improve robustness of treatment plans. Methods: IMPT plans were generated for a typical prostate patient. Nine dose distributions are computed — the nominal one and one each for ±5mm setup uncertainties along three cardinal axes and for ±3.5% range uncertainty. These nine dose distributions are supplied to the solver CPLEX as chance constraints to explicitly control plan robustness under these representative uncertainty scenarios withmore » certain probability. This probability is determined by the tolerance level. We make the chance-constrained model tractable by converting it to a mixed integer optimization problem. The quality of plans derived from this method is evaluated using dose-volume histogram (DVH) indices such as tumor dose homogeneity (D5% – D95%) and coverage (D95%) and normal tissue sparing like V70 of rectum, V65, and V40 of bladder. We also compare the results from this novel method with the conventional PTV-based method to further demonstrate its effectiveness Results: Our model can yield clinically acceptable plans within 50 seconds. The chance-constrained optimization produces IMPT plans with comparable target coverage, better target dose homogeneity, and better normal tissue sparing compared to the PTV-based optimization [D95% CTV: 67.9 vs 68.7 (Gy), D5% – D95% CTV: 11.9 vs 18 (Gy), V70 rectum: 0.0 % vs 0.33%, V65 bladder: 2.17% vs 9.33%, V40 bladder: 8.83% vs 21.83%]. It also simultaneously makes the plan more robust [Width of DVH band at D50%: 2.0 vs 10.0 (Gy)]. The tolerance level may be varied to control the tradeoff between plan robustness and quality. Conclusion: The chance-constrained optimization generates superior IMPT plan compared to the PTV-based optimization with explicit control of plan robustness. NIH/NCI K25CA168984, Eagles Cancer Research Career Development, The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, Mayo ASU Seed Grant, and The Kemper Marley Foundation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lau, A; Chen, Y; Ahmad, S

Purpose: Proton therapy exhibits several advantages over photon therapy due to depth-dose distributions from proton interactions within the target material. However, uncertainties associated with protons beam range in the patient limit the advantage of proton therapy applications. To quantify beam range, positron-emitting nuclei (PEN) and prompt gamma (PG) techniques have been developed. These techniques use de-excitation photons to describe the location of the beam in the patient. To develop a detector system for implementing the PG technique for range verification applications in proton therapy, we studied the yields, energy and angular distributions of the secondary particles emitted from a PMMAmore » phantom. Methods: Proton pencil beams of various energies incident onto a PMMA phantom with dimensions of 5 x 5 x 50 cm3 were used for simulation with the Geant4 toolkit using the standard electromagnetic packages as well as the packages based on the binary-cascade nuclear model. The emitted secondary particles are analyzed . Results: For 160 MeV incident protons, the yields of secondary neutrons and photons per 100 incident protons were ~6 and ~15 respectively. Secondary photon energy spectrum showed several energy peaks in the range between 0 and 10 MeV. The energy peaks located between 4 and 6 MeV were attributed to originate from direct proton interactions with 12C (~ 4.4 MeV) and 16O (~ 6 MeV), respectively. Most of the escaping secondary neutrons were found to have energies between 10 and 100 MeV. Isotropic emissions were found for lower energy neutrons (<10 MeV) and photons for all energies, while higher energy neutrons were emitted predominantly in the forward direction. The yields of emitted photons and neutrons increased with the increase of incident proton energies. Conclusions: A detector system is currently being developed incorporating the yields, energy and angular distributions of secondary particles from proton interactions obtained from this study.« less

Comparison of linear and nonlinear programming approaches for "worst case dose" and "minmax" robust optimization of intensity-modulated proton therapy dose distributions.

PubMed

Zaghian, Maryam; Cao, Wenhua; Liu, Wei; Kardar, Laleh; Randeniya, Sharmalee; Mohan, Radhe; Lim, Gino

2017-03-01

Robust optimization of intensity-modulated proton therapy (IMPT) takes uncertainties into account during spot weight optimization and leads to dose distributions that are resilient to uncertainties. Previous studies demonstrated benefits of linear programming (LP) for IMPT in terms of delivery efficiency by considerably reducing the number of spots required for the same quality of plans. However, a reduction in the number of spots may lead to loss of robustness. The purpose of this study was to evaluate and compare the performance in terms of plan quality and robustness of two robust optimization approaches using LP and nonlinear programming (NLP) models. The so-called "worst case dose" and "minmax" robust optimization approaches and conventional planning target volume (PTV)-based optimization approach were applied to designing IMPT plans for five patients: two with prostate cancer, one with skull-based cancer, and two with head and neck cancer. For each approach, both LP and NLP models were used. Thus, for each case, six sets of IMPT plans were generated and assessed: LP-PTV-based, NLP-PTV-based, LP-worst case dose, NLP-worst case dose, LP-minmax, and NLP-minmax. The four robust optimization methods behaved differently from patient to patient, and no method emerged as superior to the others in terms of nominal plan quality and robustness against uncertainties. The plans generated using LP-based robust optimization were more robust regarding patient setup and range uncertainties than were those generated using NLP-based robust optimization for the prostate cancer patients. However, the robustness of plans generated using NLP-based methods was superior for the skull-based and head and neck cancer patients. Overall, LP-based methods were suitable for the less challenging cancer cases in which all uncertainty scenarios were able to satisfy tight dose constraints, while NLP performed better in more difficult cases in which most uncertainty scenarios were hard to meet tight dose limits. For robust optimization, the worst case dose approach was less sensitive to uncertainties than was the minmax approach for the prostate and skull-based cancer patients, whereas the minmax approach was superior for the head and neck cancer patients. The robustness of the IMPT plans was remarkably better after robust optimization than after PTV-based optimization, and the NLP-PTV-based optimization outperformed the LP-PTV-based optimization regarding robustness of clinical target volume coverage. In addition, plans generated using LP-based methods had notably fewer scanning spots than did those generated using NLP-based methods. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Electron Nuclear Dynamics Simulations of Proton Cancer Therapy Reactions: Water Radiolysis and Proton- and Electron-Induced DNA Damage in Computational Prototypes.

PubMed

Teixeira, Erico S; Uppulury, Karthik; Privett, Austin J; Stopera, Christopher; McLaurin, Patrick M; Morales, Jorge A

2018-05-06

Proton cancer therapy (PCT) utilizes high-energy proton projectiles to obliterate cancerous tumors with low damage to healthy tissues and without the side effects of X-ray therapy. The healing action of the protons results from their damage on cancerous cell DNA. Despite established clinical use, the chemical mechanisms of PCT reactions at the molecular level remain elusive. This situation prevents a rational design of PCT that can maximize its therapeutic power and minimize its side effects. The incomplete characterization of PCT reactions is partially due to the health risks associated with experimental/clinical techniques applied to human subjects. To overcome this situation, we are conducting time-dependent and non-adiabatic computer simulations of PCT reactions with the electron nuclear dynamics (END) method. Herein, we present a review of our previous and new END research on three fundamental types of PCT reactions: water radiolysis reactions, proton-induced DNA damage and electron-induced DNA damage. These studies are performed on the computational prototypes: proton + H₂O clusters, proton + DNA/RNA bases and + cytosine nucleotide, and electron + cytosine nucleotide + H₂O. These simulations provide chemical mechanisms and dynamical properties of the selected PCT reactions in comparison with available experimental and alternative computational results.

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

NASA Astrophysics Data System (ADS)

Pettersen, H. E. S.; Alme, J.; Biegun, A.; van den Brink, A.; Chaar, M.; Fehlker, D.; Meric, I.; Odland, O. H.; Peitzmann, T.; Rocco, E.; Ullaland, K.; Wang, H.; Yang, S.; Zhang, C.; Röhrich, D.

2017-07-01

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeter was originally designed for the reconstruction of high-energy electromagnetic showers for the ALICE-FoCal project. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter concept. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. High energy protons traversing the detector leave a track through the sensor layers. These tracks are spread out through charge diffusion processes. A charge diffusion model is applied for acquisition of estimates of the deposited energy of the protons in each sensor layer by using the size of the charge diffused area. A model fit of the Bragg Curve is applied to each reconstructed track and through this, estimating the residual range of each proton. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to handle an effective proton frequency of 1 MHz by using 500 concurrent proton tracks in each readout frame, which is at the high end range of present similar prototypes. A future further optimized prototype will enable a high-speed and more accurate determination of the ranges of individual protons in a therapeutic beam.

Luminescence imaging of water during proton-beam irradiation for range estimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Seiichi, E-mail: s-yama@met.nagoya-u.ac.jp; Okumura, Satoshi; Komori, Masataka

Purpose: Proton therapy has the ability to selectively deliver a dose to the target tumor, so the dose distribution should be accurately measured by a precise and efficient method. The authors found that luminescence was emitted from water during proton irradiation and conjectured that this phenomenon could be used for estimating the dose distribution. Methods: To achieve more accurate dose distribution, the authors set water phantoms on a table with a spot scanning proton therapy system and measured the luminescence images of these phantoms with a high-sensitivity, cooled charge coupled device camera during proton-beam irradiation. The authors imaged the phantomsmore » of pure water, fluorescein solution, and an acrylic block. Results: The luminescence images of water phantoms taken during proton-beam irradiation showed clear Bragg peaks, and the measured proton ranges from the images were almost the same as those obtained with an ionization chamber. Furthermore, the image of the pure-water phantom showed almost the same distribution as the tap-water phantom, indicating that the luminescence image was not related to impurities in the water. The luminescence image of the fluorescein solution had ∼3 times higher intensity than water, with the same proton range as that of water. The luminescence image of the acrylic phantom had a 14.5% shorter proton range than that of water; the proton range in the acrylic phantom generally matched the calculated value. The luminescence images of the tap-water phantom during proton irradiation could be obtained in less than 2 s. Conclusions: Luminescence imaging during proton-beam irradiation is promising as an effective method for range estimation in proton therapy.« less

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center.

PubMed

Chung, Kwangzoo; Han, Youngyih; Kim, Jinsung; Ahn, Sung Hwan; Ju, Sang Gyu; Jung, Sang Hoon; Chung, Yoonsun; Cho, Sungkoo; Jo, Kwanghyun; Shin, Eun Hyuk; Hong, Chae-Seon; Shin, Jung Suk; Park, Seyjoon; Kim, Dae-Hyun; Kim, Hye Young; Lee, Boram; Shibagaki, Gantaro; Nonaka, Hideki; Sasai, Kenzo; Koyabu, Yukio; Choi, Changhoon; Huh, Seung Jae; Ahn, Yong Chan; Pyo, Hong Ryull; Lim, Do Hoon; Park, Hee Chul; Park, Won; Oh, Dong Ryul; Noh, Jae Myung; Yu, Jeong Il; Song, Sanghyuk; Lee, Ji Eun; Lee, Bomi; Choi, Doo Ho

2015-12-01

The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Proton Beam Therapy for Hepatocellular Carcinoma Located Adjacent to the Alimentary Tract;Proton beam therapy; Hepatocellular carcinoma; Gastrointestinal bleeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakayama, Hidetsugu; Sugahara, Shinji; Department of Radiation Oncology, Tokyo Medical University, Tokyo

2011-07-15

Purpose: To evaluate the safety and effectiveness of proton beam therapy for hepatocellular carcinoma (HCC) located adjacent to the alimentary tract. Patients and Methods: Forty-seven patients (median age, 69 years; range, 43-82 years) who had HCC located within 2 cm of the alimentary tract underwent proton beam therapy. Liver damage according to the Child-Pugh classification was Class A in 35 patients, Class B in 9, and Class C in 3. Treatment protocols of the early 16 patients and the late 31 patients were 72.6 GyE in 22 fractions and 77 GyE in 35 fractions, respectively. Results: During the median follow-upmore » period of 23 months, 24 patients died; the remaining 23 patients were alive until September 2008. The median overall survival was 33.9 months (95% confidence interval [CI], 10.8-57.0 months). Actuarial overall and local progression-free survival rates at 3 years were 50.0% and 88.1%, respectively. Grade 2 and 3 alimentary tract hemorrhage was observed in 3 (6.4%) and 1 (2.1%) patients, respectively. Conclusions: Our proton beam therapy strategy for HCC located adjacent to the alimentary tract seems to be effective but should be performed with caution.« less

A proton therapy model using discrete difference equations with an example of treating hepatocellular carcinoma.

PubMed

Bodine, Erin N; Monia, K Lars

2017-08-01

Proton therapy is a type of radiation therapy used to treat cancer. It provides more localized particle exposure than other types of radiotherapy (e.g., x-ray and electron) thus reducing damage to tissue surrounding a tumor and reducing unwanted side effects. We have developed a novel discrete difference equation model of the spatial and temporal dynamics of cancer and healthy cells before, during, and after the application of a proton therapy treatment course. Specifically, the model simulates the growth and diffusion of the cancer and healthy cells in and surrounding a tumor over one spatial dimension (tissue depth) and the treatment of the tumor with discrete bursts of proton radiation. We demonstrate how to use data from in vitro and clinical studies to parameterize the model. Specifically, we use data from studies of Hepatocellular carcinoma, a common form of liver cancer. Using the parameterized model we compare the ability of different clinically used treatment courses to control the tumor. Our results show that treatment courses which use conformal proton therapy (targeting the tumor from multiple angles) provides better control of the tumor while using lower treatment doses than a non-conformal treatment course, and thus should be recommend for use when feasible.

Potential of Proton Therapy to Reduce Acute Hematologic Toxicity in Concurrent Chemoradiation Therapy for Esophageal Cancer.

PubMed

Warren, Samantha; Hurt, Christopher N; Crosby, Thomas; Partridge, Mike; Hawkins, Maria A

2017-11-01

Radiation therapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumor control in esophageal cancer; however, any increase in acute hematologic toxicity (HT) could limit the predicted improvement in patient outcomes. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy. Therefore, we investigated the potential of bone marrow sparing with protons for esophageal tumors. Twenty-one patients with mid-esophageal cancer who had undergone conformal radiation therapy (3D50) were selected. Two surrogates for bone marrow were created by outlining the thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse. The percentage of overlap of the TV with the planning treatment volume was recorded for each patient. Additional plans were created retrospectively, including a volumetric modulated arc therapy (VMAT) plan with the same dose as for 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high-risk subregion within the planning treatment volume; a reoptimized TV-sparing VMAT plan; and a proton therapy plan with the same SIB dose prescription. The bone and TV dose metrics were recorded and compared across all plans and variations with respect to PTV and percentage of overlap for each patient. The 3D50 plans showed the highest bone mean dose and TV percentage of volume receiving ≥30 Gy (V 30Gy ) for each patient. The VMAT plans irradiated a larger bone V 10Gy than did the 3D50 plans. The reoptimized VMAT62.5 VT plans showed improved sparing of the TV volume, but only the proton plans showed significant sparing for bone V 10Gy and bone mean dose, especially for patients with a larger PTV. The results of the present study have shown that proton therapy can reduced bone marrow toxicity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

WE-H-BRA-01: BEST IN PHYSICS (THERAPY): Nano-Dosimetric Kinetic Model for Variable Relative Biological Effectiveness of Proton and Ion Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abolfath, R; Bronk, L; Titt, U.

2016-06-15

Purpose: Recent clonogenic cell survival and γH2AX studies suggest proton relative biological effectiveness (RBE) may be a non-linear function of linear energy transfer (LET) in the distal edge of the Bragg peak and beyond. We sought to develop a multiscale model to account for non-linear response phenomena to aid in the optimization of intensity-modulated proton therapy. Methods: The model is based on first-principle simulations of proton track structures, including secondary ions, and an analytical derivation of the dependence on particle LET of the linear-quadratic (LQ) model parameters α and β. The derived formulas are an extension of the microdosimetric kineticmore » (MK) model that captures dissipative track structures and non-Poissonian distribution of DNA damage at the distal edge of the Bragg peak and beyond. Monte Carlo simulations were performed to confirm the non-linear dose-response characteristics arising from the non-Poisson distribution of initial DNA damage. Results: In contrast to low LET segments of the proton depth dose, from the beam entrance to the Bragg peak, strong deviations from non-dissipative track structures and Poisson distribution in the ionization events in the Bragg peak distal edge govern the non-linear cell response and result in the transformation α=(1+c-1 L) α-x+2(c-0 L+c-2 L^2 )(1+c-1 L) β-x and β=(1+c-1 L)^2 β-x. Here L is the charged particle LET, and c-0,c-1, and c-2 are functions of microscopic parameters and can be served as fitting parameters to the cell-survival data. In the low LET limit c-1, and c-2 are negligible hence the linear model proposed and used by Wilkins-Oelfke for the proton treatment planning system can be retrieved. The present model fits well the recent clonogenic survival data measured recently in our group in MDACC. Conclusion: The present hybrid method provides higher accuracy in calculating the RBE-weighted dose in the target and normal tissues.« less

Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, R. Charles, E-mail: rnichols@floridaproton.org; University of Florida Proton Therapy Institute, Jacksonville, FL; Morris, Christopher G.

Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. Themore » pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.« less

The technical implementation of an IMPT system for research purpose

NASA Astrophysics Data System (ADS)

Nguyen, T. T. C.; Nguyen, B. T.; Mai, N. V.

2018-03-01

Because of their superior distribution, proton beams is the state-of-the-art modality in radiation therapy. There is a variety of researchers about proton therapy to utilize it. In this paper, we introduce a Matlab-based platform to develop and prototype proton treatment planning using LAP and CERR. Planning workflow to make an IMPT plan is described in details and demonstrated by a prostate case. The results showed that most of the dose criteria are satisfied, except for bladder and rectum, 2% of the volume of each organ receiving the least dose of 77.5 Gy (RBE) instead of 76 Gy(RBE) as dose requirements suggested by ICRU 78. As a result, planners absolutely can implement Intensity Modulated Proton Therapy plans by LAP and CERR for research purpose.

Using a knowledge-based planning solution to select patients for proton therapy.

PubMed

Delaney, Alexander R; Dahele, Max; Tol, Jim P; Kuijper, Ingrid T; Slotman, Ben J; Verbakel, Wilko F A R

2017-08-01

Patient selection for proton therapy by comparing proton/photon treatment plans is time-consuming and prone to bias. RapidPlan™, a knowledge-based-planning solution, uses plan-libraries to model and predict organ-at-risk (OAR) dose-volume-histograms (DVHs). We investigated whether RapidPlan, utilizing an algorithm based only on photon beam characteristics, could generate proton DVH-predictions and whether these could correctly identify patients for proton therapy. Model PROT and Model PHOT comprised 30 head-and-neck cancer proton and photon plans, respectively. Proton and photon knowledge-based-plans (KBPs) were made for ten evaluation-patients. DVH-prediction accuracy was analyzed by comparing predicted-vs-achieved mean OAR doses. KBPs and manual plans were compared using salivary gland and swallowing muscle mean doses. For illustration, patients were selected for protons if predicted Model PHOT mean dose minus predicted Model PROT mean dose (ΔPrediction) for combined OARs was ≥6Gy, and benchmarked using achieved KBP doses. Achieved and predicted Model PROT /Model PHOT mean dose R 2 was 0.95/0.98. Generally, achieved mean dose for Model PHOT /Model PROT KBPs was respectively lower/higher than predicted. Comparing Model PROT /Model PHOT KBPs with manual plans, salivary and swallowing mean doses increased/decreased by <2Gy, on average. ΔPrediction≥6Gy correctly selected 4 of 5 patients for protons. Knowledge-based DVH-predictions can provide efficient, patient-specific selection for protons. A proton-specific RapidPlan-solution could improve results. Copyright © 2017 Elsevier B.V. All rights reserved.

SU-F-BRD-01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity-Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Shen, J; Stoker, J

2015-06-15

Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses tomore » achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest compared to TV. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research; Mayo ASU Seed Grant; The Kemper Marley Foundation.« less

SU-E-T-435: Development and Commissioning of a Complete System for In-Vivo Dosimetry and Range Verification in Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samuel, D; Testa, M; Park, Y

Purpose: In-vivo dose and beam range verification in proton therapy could play significant roles in proton treatment validation and improvements. Invivo beam range verification, in particular, could enable new treatment techniques one of which, for example, could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. We have developed and commissioned an integrated system with hardware, software and workflow protocols, to provide a complete solution, simultaneously for both in-vivo dosimetry and range verification for proton therapy. Methods: The system uses a matrix of diodes, up to 12 in total, but separablemore » into three groups for flexibility in application. A special amplifier was developed to capture extremely small signals from very low proton beam current. The software was developed within iMagX, a general platform for image processing in radiation therapy applications. The range determination exploits the inherent relationship between the internal range modulation clock of the proton therapy system and the radiological depth at the point of measurement. The commissioning of the system, for in-vivo dosimetry and for range verification was separately conducted using anthropomorphic phantom. EBT films and TLDs were used for dose comparisons and range scan of the beam distal fall-off was used as ground truth for range verification. Results: For in-vivo dose measurement, the results were in agreement with TLD and EBT films and were within 3% from treatment planning calculations. For range verification, a precision of 0.5mm is achieved in homogeneous phantoms, and a precision of 2mm for anthropomorphic pelvic phantom, except at points with significant range mixing. Conclusion: We completed the commissioning of our system for in-vivo dosimetry and range verification in proton therapy. The results suggest that the system is ready for clinical trials on patient.« less

EFFECT OF CYP2C19 GENETIC POLYMORPHISMS ON THE EFFICACY OF PROTON PUMP INHIBITOR-BASED TRIPLE ERADICATION THERAPY IN SLAVIC PATIENTS WITH PEPTIC ULCERS: A META-ANALYSIS.

PubMed

Denisenko, N P; Sychev, D A; Sizova, Zh M; Rozhkov, A V; Kondrashov, A V

Several meta-analyzes reported the effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication. Most of the studies which were included in these meta-analyzes were held on Asian population. Thus, there is lack of information about the effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients with peptic ulcers. The aim of the study - to determine whether CYP2C19 affect the efficacy of proton pump inhibitor-based triple eradica- tion therapy in Slavic patients with peptic ulcers. Data search was performed using Russian index of scientific citation database, Google Scholar and MEDLINE PubMed. Statistics was held in Review Manager v 5.3. The odds ratio (OR) and 95% confidence interval (95% Cl) for eradication of H.pylori was estimated in a fixed-effect model when no heterogeneity across the studies was indicated. Four articles published between 2008 and 2015 were included in meta-analysis (three Russian studies, one Polish study). Eradication rates were significantly lower in CYP2C19 extensive metabolizers of proton pump inhibitors than in a combined group of intermediate and poor metabolizers (OR = 1,90, CI-95% 1,08-3,34, p = 0,03; heterogeneity: 12= 0%, p = 0,74). We also found that proton pump inhibitor-based triple eradication therapy achieved higher rates in poor metabolizers than in a combined group of intermediate and extensive metabolizers of CYP2C19 (OR= 5,48 CI-95% 1,51-19,93, p = 0,01; heterogeneity: F= 0%, p = 0,66). The impact of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients appears significant.

Health economic controversy and cost-effectiveness of proton therapy.

PubMed

Lievens, Yolande; Pijls-Johannesma, Madelon

2013-04-01

Owing to increasing healthcare costs, there is a need to examine whether the benefits of new technologies are worth the extra cost. In proton therapy, where the evidence in favor is limited, it is heavily debated whether the expected benefit justifies the higher capital and operating costs. The aim of this article was to explore the existing methodologies of economic evaluations (EEs) of particle therapy and recommend an approach for future data collection and analysis. We reviewed the published literature on health economics of proton therapy using accepted guidelines on performing EE. Different cost strategies were assessed and comparisons with other treatment modalities were made in terms of cost-effectiveness. Potential bias in the existing studies was identified and new methodologies proposed. The principal cause of bias in EEs of proton therapy is the lack of valid data on effects as well as costs. The introduction of proton therapy may be seriously hampered by the lack of outcome and cost data and the situation is likely to continue not only in terms of justifying the capital investment but also covering the operational costs. We identified an urgent need to collect appropriate data to allow for reimbursement of such novel technology. In the absence of level 1 evidence, well-performed modeling studies taking into account the available cost and outcome parameters, including the current uncertainties, can help to address the problem of limited outcome and health economic data. The approach of coverage with evidence development, in which evidence is collected in an ongoing manner in population-based registries along with dedicated financing, may allow technological advances with limited initial evidence of benefit and value, such as protons, to become available to patients in an early phase of their technology life cycle. Copyright © 2013 Elsevier Inc. All rights reserved.

Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.

PubMed

Vaduganathan, Muthiah; Bhatt, Deepak L; Cryer, Byron L; Liu, Yuyin; Hsieh, Wen-Hua; Doros, Gheorghe; Cohen, Marc; Lanas, Angel; Schnitzer, Thomas J; Shook, Thomas L; Lapuerta, Pablo; Goldsmith, Mark A; Laine, Loren; Cannon, Christopher P

2016-04-12

The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

SU-F-T-146: Comparing Monte Carlo Simulations with Commissioning Beam Data for Mevion S250 Proton Therapy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prusator, M; Jin, H; Ahmad, S

2016-06-15

Purpose: To evaluate the Monte Carlo simulated beam data with the measured commissioning data for the Mevion S250 proton therapy system. Method: The Mevion S250 proton therapy system utilizes a passive double scattering technique with a unique gantry mounted superconducting accelerator and offers effective proton therapy in a compact design concept. The field shaping system (FSS) includes first scattering foil, range modulator wheel (RMW), second scattering foil and post absorber and offers two field sizes and a total of 24 treatment options from proton range of 5 cm to 32 cm. The treatment nozzle was modeled in detail using TOPASmore » (TOolkit for PArticle Simulation) Monte Carlo code. The timing feathers of the moving modulator wheels were also implemented to generate the Spread Out Bragg Peak (SOBP). The simulation results including pristine Bragg Peak, SOBP and dose profiles were compared with the data measured during beam commissioning. Results: The comparison between the measured data and the simulation data show excellent agreement. For pristine proton Bragg Peaks, the simulated proton range (depth of distal 90%) values agreed well with the measured range values within 1 mm accuracy. The differences of the distal falloffs (depth from distal 80% to 20%) were also found to be less than 1 mm between the simulations and measurements. For the SOBP, the widths of modulation (depth of proximal 95% to distal 90%) were also found to agree with the measurement within 1 mm. The flatness of the simulated and measured lateral profiles was found to be 0.6 % and 1.1 %, respectively. Conclusion: The agreement between simulations and measurements demonstrate that TOPAS could be used as a viable platform to proton therapy applications. The matched simulation results offer a great tool and open opportunity for variety of applications.« less

Minimizing treatment planning errors in proton therapy using failure mode and effects analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Yuanshui, E-mail: yuanshui.zheng@okc.procure.com; Johnson, Randall; Larson, Gary

Purpose: Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. Methods: The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authorsmore » estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. Results: In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. Conclusions: The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their clinic have proven to be useful in error reduction in proton treatment planning, thus improving the effectiveness and safety of proton therapy.« less

Minimizing treatment planning errors in proton therapy using failure mode and effects analysis.

PubMed

Zheng, Yuanshui; Johnson, Randall; Larson, Gary

2016-06-01

Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their clinic have proven to be useful in error reduction in proton treatment planning, thus improving the effectiveness and safety of proton therapy.

[Initial experience of proton beam therapy at the new facility of the University of Tsukuba].

PubMed

Kagei, Kenji; Tokuuye, Koichi; Sugahara, Shinji; Hata, Masaharu; Igaki, Hiroshi; Hashimoto, Takayuki; Ohara, Kiyoshi; Akine, Yasuyuki

2004-05-01

To present the initial experience with proton beam therapy at the new Proton Medical Research Center (PMRC) of the University of Tsukuba. The new facility has a synchrotron with maximum energy of 250MeV and two rotational gantries. We treated 105 patients with 120 lesions with proton beams in the first year, beginning in September 2001. The most common lesion treated was primary liver cancer (40 lesions) followed by lung cancer, head and neck cancers, and prostate cancer. Concurrent X-ray radiotherapy was given for 38 of the 120 lesions. The median follow-up period was 11 months (range, 1-19 months). Of the 105 patients, 97% had Grade 0-2 RTOG/EORTC acute morbidities, while the remaining 3% had Grade 3. Tumor response after irradiation was CR for 35% of the lesions, PR for 25%, SD for 22%, PD for 9%, and not evaluated for 9%. The proton beam therapy conducted at the new facility of the University of Tsukuba was safe and effective.

Aspirin and proton pump inhibitor combination therapy for prevention of cardiovascular disease and Barrett's esophagus.

PubMed

Peura, David A; Wilcox, C Mel

2014-01-01

Aspirin, used at low doses (75-325 mg daily), prevents aggregation of platelets and is prescribed for patients as pharmacologic prevention of cardiovascular disease. Despite the well-documented beneficial effects of aspirin, prolonged use is associated with damage to the gastrointestinal (GI) mucosa in the upper and lower GI tract. Patient risk of hemorrhage and peptic ulcer formation is increased with older age, previous ulcer history, Helicobacter pylori infection, and concomitant use of nonsteroidal anti-inflammatory drugs, corticosteroids, or antithrombotic agents. As termination of aspirin therapy can precipitate a cardiovascular event, patients at risk need co-therapy with gastroprotective agents, such as proton pump inhibitors (PPIs), to reduce the GI side effects of aspirin treatment. Fixed-dose combinations of low-dose aspirin and gastroprotective agents have been designed to increase medication compliance, improve clinical outcomes, and reduce the overall cost of therapy. Prolonged use of PPIs may, however, lead to serious adverse effects or, in some cases, reduce the cardioprotective effects of aspirin. Hence, physicians need to carefully consider the benefits and risks associated with the condition of each patient to optimize clinical outcomes of combination therapy. A growing body of clinical evidence indicates that aspirin may decrease the risk of colorectal and other GI cancers, as well as reduce progression from Barrett's esophagus (BE) to esophageal adenocarcinoma. Furthermore, PPIs have recently been shown to reduce neoplastic transformation in patients with BE. Thus, the use of a fixed-dose aspirin/PPI combination could potentially provide chemopreventive benefit to patients with BE, and, at the same time, treat the underlying gastroesophageal reflux responsible for the condition.

Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study.

PubMed

Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

2012-03-27

Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1-7.2. Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1-7.2 is most promising.

Proton Therapy for Thoracoabdominal Tumors

NASA Astrophysics Data System (ADS)

Sakurai, Hideyuki; Okumura, Toshiyuki; Sugahara, Shinji; Nakayama, Hidetsugu; Tokuuye, Koichi

In advanced-stage disease of certain thoracoabdominal tumors, proton therapy (PT) with concurrent chemotherapy may be an option to reduce side effects. Several technological developments, including a respiratory gating system and implantation of fiducial markers for image guided radiation therapy (IGRT), are necessary for the treatment in thoracoabdominal tumors. In this chapter, the role of PT for tumors of the lung, the esophagus, and liver are discussed.

WE-G-BRE-07: Proton Therapy Enhanced by Tumor-Targeting Gold Nanoparticles: A Pilot in Vivo Experiment at The Proton Therapy Center at MD Anderson Cancer Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfe, T; Grant, J; Wolfe, A

Purpose: Assess tumor-growth delay and survival in a mouse model of prostate cancer treated with tumor-targeting gold nanoparticles (AuNPs) and proton therapy. Methods: We first examined the accumulation of targeting nanoparticles within prostate tumors by imaging AuNPs with ultrasound-guided photoacoustics at 24h after the intravenous administration of goserelin-conjugated AuNPs (gAuNP) in three mice. Nanoparticles were also imaged at the cellular level with TEM in PC3 cells incubated with gAuNP for 24h. Pegylated AuNPs (pAuNP) were also imaged in vivo and in vitro for comparison. PC3 cells were then implanted subcutaneously in nude mice; 51mice with 8–10mm tumors were included. AuNPsmore » were injected intravenously at 0.2%w/w final gold concentration 24h before irradiation. A special jig was designed to facilitate tumor irradiation perpendicular to the proton beam. Proton energy was set to 180MeV, the radiation field was 18×18cm{sup 2}, and 9cm or 13.5cm thick solid-water compensators were used to position the tumors at either the beam entrance (BE) or the SOBP. Physical doses of 5Gy were delivered to all tumors on a patient beam line at MD Anderson's Proton Therapy Center. Results: The photoacoustic experiment reveled that our nanoparticles leak from the tumor-feeding vasculature and accumulate within the tumor volume over time. Additionally, TEM images showed gAuNP are internalized in cancer cells, accumulating within the cytoplasm, whereas pAuNP are not. Tumor-growth was delayed by 11 or 32days in mice receiving gAuNP irradiated at the BE or the SOBP, relative to proton radiation alone. Survival curves (ongoing experiment) reveal that gAuNPs improved survival by 36% or 74% for tumors irradiated at the BE or SOBP. Conclusion: These important, albeit preliminary, in vivo findings reveal nanoparticles to be potent sensitizers to proton therapy. Further, conjugation of AuNPs to tumor-specific antigens that promote enhanced cellular internalization improved both tumor-growth delay and survival of mice after proton therapy.« less

Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

NASA Astrophysics Data System (ADS)

Fontenot, Jonas; Taddei, Phillip; Zheng, Yuanshui; Mirkovic, Dragan; Jordan, Thomas; Newhauser, Wayne

2008-03-01

Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy-1. Sensitivity analysis revealed that E/D varied by ±30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy-1 in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy-1 in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center

PubMed Central

Chung, Kwangzoo; Kim, Jinsung; Ahn, Sung Hwan; Ju, Sang Gyu; Jung, Sang Hoon; Chung, Yoonsun; Cho, Sungkoo; Jo, Kwanghyun; Shin, Eun Hyuk; Hong, Chae-Seon; Shin, Jung Suk; Park, Seyjoon; Kim, Dae-Hyun; Kim, Hye Young; Lee, Boram; Shibagaki, Gantaro; Nonaka, Hideki; Sasai, Kenzo; Koyabu, Yukio; Choi, Changhoon; Huh, Seung Jae; Ahn, Yong Chan; Pyo, Hong Ryull; Lim, Do Hoon; Park, Hee Chul; Park, Won; Oh, Dong Ryul; Noh, Jae Myung; Yu, Jeong Il; Song, Sanghyuk; Lee, Ji Eun; Lee, Bomi; Choi, Doo Ho

2015-01-01

Purpose The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. Materials and Methods The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. Results The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. Conclusion The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015. PMID:26756034

Monte Carlo simulation of prompt γ-ray emission in proton therapy using a specific track length estimator

NASA Astrophysics Data System (ADS)

El Kanawati, W.; Létang, J. M.; Dauvergne, D.; Pinto, M.; Sarrut, D.; Testa, É.; Freud, N.

2015-10-01

A Monte Carlo (MC) variance reduction technique is developed for prompt-γ emitters calculations in proton therapy. Prompt-γ emitted through nuclear fragmentation reactions and exiting the patient during proton therapy could play an important role to help monitoring the treatment. However, the estimation of the number and the energy of emitted prompt-γ per primary proton with MC simulations is a slow process. In order to estimate the local distribution of prompt-γ emission in a volume of interest for a given proton beam of the treatment plan, a MC variance reduction technique based on a specific track length estimator (TLE) has been developed. First an elemental database of prompt-γ emission spectra is established in the clinical energy range of incident protons for all elements in the composition of human tissues. This database of the prompt-γ spectra is built offline with high statistics. Regarding the implementation of the prompt-γ TLE MC tally, each proton deposits along its track the expectation of the prompt-γ spectra from the database according to the proton kinetic energy and the local material composition. A detailed statistical study shows that the relative efficiency mainly depends on the geometrical distribution of the track length. Benchmarking of the proposed prompt-γ TLE MC technique with respect to an analogous MC technique is carried out. A large relative efficiency gain is reported, ca. 105.

Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

PubMed

Niedzielski, Joshua S; Yang, Jinzhong; Mohan, Radhe; Titt, Uwe; Mirkovic, Dragan; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel R; Martel, Mary K; Briere, Tina M; Court, Laurence E

2017-11-15

To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer. A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment. Differences between the 2 modalities were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis analysis of variance), as well as the incidence and severity of esophagitis grade (χ 2 and Fisher exact tests, respectively). The dose-response of the imaging biomarker was also compared between modalities using esophageal equivalent uniform dose, as well as delivered dose to an isotropic esophageal subvolume. No statistically significant difference in the distribution of esophagitis grade, the incidence of grade ≥3 esophagitis (15 and 11 patients treated with IMRT and proton therapy, respectively), or the esophageal expansion imaging biomarker between cohorts (P>.05) was found. The distribution of imaging biomarker metric values had similar distributions between treatment arms, despite a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose-response was similar between modalities for dose quantified as esophageal equivalent uniform dose and delivered esophageal subvolume dose. Regardless of treatment modality, there was high variability in imaging biomarker response, as well as esophagitis grade, for similar esophageal doses between patients. There was no significant difference in esophageal toxicity from either proton- or photon-based radiation therapy as quantified by esophagitis grade or the esophageal expansion imaging biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-F-T-197: Investigating Optimal Oblique-Beam Arrangement for Bilateral Metallic Prosthesis Prostate Cancer in Pencil Beam Scanning Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rana, S; Tesfamicael, B; Park, S

Purpose: The main purpose of this study is to investigate the optimum oblique-beam arrangement for bilateral metallic prosthesis prostate cancer treatment in pencil beam scanning (PBS) proton therapy. Methods: A computed tomography dataset of bilateral metallic prosthesis prostate cancer case was selected for this retrospective study. A total of four beams (rightanterior- oblique [RAO], left-anterior-oblique [LAO], left-posterior-oblique [LPO], and right-posterior-oblique [RPO]) were selected for treatment planning. PBS plans were generated using multi-field-optimization technique for a total dose of 79.2 Gy[RBE] to be delivered in 44 fractions. Specifically, five different PBS plans were generated based on 2.5% ± 2 mm rangemore » uncertainty using five different beam arrangements (i)LAO+RAO+LPO+RPO, (ii)LAO+RAO, (iii)LPO+RPO, (iv)RAO+LPO, and (v)LAO+RPO. Each PBS plan was optimized by applying identical dose-volume constraints to the PTV, rectum, and bladder. Treatment plans were then compared based on the dose-volume histograms results. Results: The PTV coverage was found to be greater than 99% in all five plans. The homogeneity index (HI) was found to be almost identical (range, 0.03–0.04). The PTV mean dose was found to be comparable (range, 81.0–81.1 Gy[RBE]). For the rectum, the lowest mean dose (8.0 Gy[RBE]) and highest mean dose (31.1 Gy[RBE]) were found in RAO+LAO plan and LPO+RPO plan, respectively. LAO+RAO plan produced the most favorable dosimetric results of the rectum in the medium-dose region (V50) and high-dose region (V70). For the bladder, the lowest (5.0 Gy[RBE]) and highest mean dose (10.3 Gy[RBE]) were found in LPO+RPO plan and RAO+LAO plan, respectively. Other dosimetric results (V50 and V70) of the bladder were slightly better in LPO+RPO plan than in other plans. Conclusion: Dosimetric findings from this study suggest that two anterior-oblique proton beams arrangement (LAO+RAO) is a more favorable option with the possibility of reducing rectal dose significantly while maintaining comparable target coverage and acceptable bladder dose.« less

GPU-accelerated automatic identification of robust beam setups for proton and carbon-ion radiotherapy

NASA Astrophysics Data System (ADS)

Ammazzalorso, F.; Bednarz, T.; Jelen, U.

2014-03-01

We demonstrate acceleration on graphic processing units (GPU) of automatic identification of robust particle therapy beam setups, minimizing negative dosimetric effects of Bragg peak displacement caused by treatment-time patient positioning errors. Our particle therapy research toolkit, RobuR, was extended with OpenCL support and used to implement calculation on GPU of the Port Homogeneity Index, a metric scoring irradiation port robustness through analysis of tissue density patterns prior to dose optimization and computation. Results were benchmarked against an independent native CPU implementation. Numerical results were in agreement between the GPU implementation and native CPU implementation. For 10 skull base cases, the GPU-accelerated implementation was employed to select beam setups for proton and carbon ion treatment plans, which proved to be dosimetrically robust, when recomputed in presence of various simulated positioning errors. From the point of view of performance, average running time on the GPU decreased by at least one order of magnitude compared to the CPU, rendering the GPU-accelerated analysis a feasible step in a clinical treatment planning interactive session. In conclusion, selection of robust particle therapy beam setups can be effectively accelerated on a GPU and become an unintrusive part of the particle therapy treatment planning workflow. Additionally, the speed gain opens new usage scenarios, like interactive analysis manipulation (e.g. constraining of some setup) and re-execution. Finally, through OpenCL portable parallelism, the new implementation is suitable also for CPU-only use, taking advantage of multiple cores, and can potentially exploit types of accelerators other than GPUs.

Meta-analysis: comparative efficacy of different proton-pump inhibitors in triple therapy for Helicobacter pylori eradication.

PubMed

Vergara, M; Vallve, M; Gisbert, J P; Calvet, X

2003-09-15

It is not known whether certain proton-pump inhibitors are more efficacious than others when used in triple therapy for Helicobacter pylori eradication. To compare the efficacy of different proton-pump inhibitors in triple therapy by performing a meta-analysis. A MEDLINE search was performed. Abstracts of the European Helicobacter pylori Study Group and the American Gastroenterological Association congresses from 1996 to 2002 were also examined. Randomized studies with at least two branches of triple therapy that differed only in terms of type of proton-pump inhibitor were included in a meta-analysis using Review Manager 4.1. Fourteen studies were included. Intention-to-treat cure rates were similar for omeprazole and lansoprazole: 74.7% vs. 76%, odds ratio (OR) 0.91 [95% confidence interval (CI) 0.69-1.21] in a total of 1085 patients; for omeprazole and rabeprazole: 77.9% vs. 81.2%, OR 0.81 (95% CI 0.58-1.15) in a total of 825 patients; for omeprazole and esomeprazole: 87.7% vs. 89%, OR 0.89 (95% CI 0.58-1.35) in 833 patients; and for lansoprazole and rabeprazole: 81% vs. 85.7%, OR 0.77 (95% CI 0.48-1.22) in 550 patients. The efficacy of various proton-pump inhibitors seems to be similar when used for H. pylori eradication in standard triple therapy.

Optimization of GATE and PHITS Monte Carlo code parameters for uniform scanning proton beam based on simulation with FLUKA general-purpose code

NASA Astrophysics Data System (ADS)

Kurosu, Keita; Takashina, Masaaki; Koizumi, Masahiko; Das, Indra J.; Moskvin, Vadim P.

2014-10-01

Although three general-purpose Monte Carlo (MC) simulation tools: Geant4, FLUKA and PHITS have been used extensively, differences in calculation results have been reported. The major causes are the implementation of the physical model, preset value of the ionization potential or definition of the maximum step size. In order to achieve artifact free MC simulation, an optimized parameters list for each simulation system is required. Several authors have already proposed the optimized lists, but those studies were performed with a simple system such as only a water phantom. Since particle beams have a transport, interaction and electromagnetic processes during beam delivery, establishment of an optimized parameters-list for whole beam delivery system is therefore of major importance. The purpose of this study was to determine the optimized parameters list for GATE and PHITS using proton treatment nozzle computational model. The simulation was performed with the broad scanning proton beam. The influences of the customizing parameters on the percentage depth dose (PDD) profile and the proton range were investigated by comparison with the result of FLUKA, and then the optimal parameters were determined. The PDD profile and the proton range obtained from our optimized parameters list showed different characteristics from the results obtained with simple system. This led to the conclusion that the physical model, particle transport mechanics and different geometry-based descriptions need accurate customization in planning computational experiments for artifact-free MC simulation.

Advanced Accelerators for Medical Applications

NASA Astrophysics Data System (ADS)

Uesaka, Mitsuru; Koyama, Kazuyoshi

We review advanced accelerators for medical applications with respect to the following key technologies: (i) higher RF electron linear accelerator (hereafter “linac”); (ii) optimization of alignment for the proton linac, cyclotron and synchrotron; (iii) superconducting magnet; (iv) laser technology. Advanced accelerators for medical applications are categorized into two groups. The first group consists of compact medical linacs with high RF, cyclotrons and synchrotrons downsized by optimization of alignment and superconducting magnets. The second group comprises laser-based acceleration systems aimed of medical applications in the future. Laser plasma electron/ion accelerating systems for cancer therapy and laser dielectric accelerating systems for radiation biology are mentioned. Since the second group has important potential for a compact system, the current status of the established energy and intensity and of the required stability are given.

Advanced Accelerators for Medical Applications

NASA Astrophysics Data System (ADS)

Uesaka, Mitsuru; Koyama, Kazuyoshi

We review advanced accelerators for medical applications with respect to the following key technologies: (i) higher RF electron linear accelerator (hereafter "linac"); (ii) optimization of alignment for the proton linac, cyclotron and synchrotron; (iii) superconducting magnet; (iv) laser technology. Advanced accelerators for medical applications are categorized into two groups. The first group consists of compact medical linacs with high RF, cyclotrons and synchrotrons downsized by optimization of alignment and superconducting magnets. The second group comprises laserbased acceleration systems aimed of medical applications in the future. Laser plasma electron/ion accelerating systems for cancer therapy and laser dielectric accelerating systems for radiation biology are mentioned. Since the second group has important potential for a compact system, the current status of the established energy and intensity and of the required stability are given.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Y; Chang, A; Liu, Y

Purpose: Electron beams are commonly used for boost radiation following whole breast irradiation (WBI) to improve the in-breast local control. Proton beams have a finite range and a sharper distal dose falloff compared to electron beams, thus potentially sparing more heart and lung in breast treatment. The purpose of the study is to compare protons with electrons for boost breast treatment in terms of target coverage and normal tissue sparing. Methods: Six breast cancer patients were included in this study. All women received WBI to 45–50 Gy, followed by a 10–16.2 Gy boost with standard fractionation. If proton beams weremore » used for the boost treatment, an electron plan was retrospectively generated for comparison using the same CT set and structures, and vice versa if electron beams were used for treatment. Proton plans were generated using the treatment planning system (TPS) with two to three uniform scanning proton beams. Electron plans were generated using the Pinnacle TPS with one single en face beam. Dose-volume histograms (DVH) were calculated and compared between proton and electron boost plans. Results: Proton plans show a similar boost target coverage, similar skin dose, and much better heart and lung sparing. For an example patient, V95% for PTV was 99.98% and skin (5 mm shell) received a max dose close to the prescription dose for both protons and electrons; however, V2 and V5 for the ipsilateral lung and heart were 37.5%, 17.9% and 19.9%, 4.9% respectively for electrons, but were essentially 0 for protons. Conclusions: This dosimetric comparison demonstrates that while both proton therapy and electron therapy provided similar coverage and skin dose, proton therapy could largely reduce the dose to lung and heart, thus leading to potential less side effects.« less

Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field

NASA Astrophysics Data System (ADS)

Paganetti, Harald; Athar, Basit S.; Moteabbed, Maryam; Adams, Judith A.; Schneider, Uwe; Yock, Torunn I.

2012-10-01

There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can significantly reduce the risk for developing an in-field second malignancy. The risk depends on treatment planning parameters, i.e. an analysis based on our formalism could be applied within treatment planning programs to guide treatment plans for pediatric patients.

Dosimetric comparison of photon and proton treatment techniques for chondrosarcoma of thoracic spine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Poonam, E-mail: yadav@humonc.wisc.edu; Department of Medical Physics, University of Wisconsin, Madison, WI; University of Wisconsin Riverview Cancer Center, Wisconsin Rapids, WI

2013-10-01

Chondrosarcomas are relatively radiotherapy resistant, and also delivering high radiation doses is not feasible owing to anatomic constraints. In this study, the feasibility of helical tomotherapy for treatment of chondrosarcoma of thoracic spine is explored and compared with other available photon and proton radiotherapy techniques in the clinical setting. A patient was treated for high-grade chondrosarcoma of the thoracic spine using tomotherapy. Retrospectively, the tomotherapy plan was compared with intensity-modulated radiation therapy, dynamic arc photon therapy, and proton therapy. Two primary comparisons were made: (1) comparison of normal tissue sparing with comparable target volume coverage (plan-1), and (2) comparison ofmore » target volume coverage with a constrained maximum dose to the cord center (plan-2). With constrained target volume coverage, proton plans were found to yield lower mean doses for all organs at risk (spinal cord, esophagus, heart, and both lungs). Tomotherapy planning resulted in the lowest mean dose to all organs at risk amongst photon-based methods. For cord dose constrained plans, the static-field intensity-modulated radiation therapy and dynamic arc plans resulted target underdosing in 20% and 12% of planning target volume2 volumes, respectively, whereas both proton and tomotherapy plans provided clinically acceptable target volume coverage with no portion of planning target volume2 receiving less than 90% of the prescribed dose. Tomotherapy plans are comparable to proton plans and produce superior results compared with other photon modalities. This feasibility study suggests that tomotherapy is an attractive alternative to proton radiotherapy for delivering high doses to lesions in the thoracic spine.« less

TU-G-BRB-05: Panel Discussion: Clinical Trials in Proton and Ion Therapy - Are We Ready?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulte, R.

2015-06-15

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. Themore » lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle clinical trial development and support. Research reported in this presentation is supported by the National Cancer Institute of the National; Institutes of Health under Award Number P20CA183640.« less

TU-G-BRB-00: Clinical Trials in Proton and Particle Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2015-06-15

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. Themore » lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle clinical trial development and support. Research reported in this presentation is supported by the National Cancer Institute of the National; Institutes of Health under Award Number P20CA183640.« less

Acid suppression and surgical therapy for Barrett's oesophagus.

PubMed

de Jonge, Pieter J F; Spaander, Manon C; Bruno, Marco J; Kuipers, Ernst J

2015-02-01

Gastro-oesophageal reflux disease is a common medical problem in developed countries, and is a risk factor for the development of Barrett's oesophagus and oesophageal adenocarcinoma. Both proton pump inhibitor therapy and antireflux surgery are effective at controlling endoscopic signs and symptoms of gastro-oesophageal reflux in patients with Barrett's oesophagus, but often fail to eliminate pathological oesophageal acid exposure. The current available studies strongly suggest that acid suppressive therapy, both pharmacological as well as surgical acid suppression, can reduce the risk the development and progression in patients with Barrett's oesophagus, but are not capable of complete prevention. No significant differences have been found between pharmacological and surgical therapy. For clinical practice, patients should be prescribed a proton pump inhibitor once daily as maintenance therapy, with the dose guided by symptoms. Antireflux surgery can be a good alternative to proton pump inhibitor therapy, but should be primarily offered to patients with symptomatic reflux, and not to asymptomatic patients with the rationale to protect against cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preliminary analysis for integration of spot-scanning proton beam therapy and real-time imaging and gating.

PubMed

Shimizu, S; Matsuura, T; Umezawa, M; Hiramoto, K; Miyamoto, N; Umegaki, K; Shirato, H

2014-07-01

Spot-scanning proton beam therapy (PBT) can create good dose distribution for static targets. However, there exists larger uncertainty for tumors that move due to respiration, bowel gas or other internal circumstances within the patients. We have developed a real-time tumor-tracking radiation therapy (RTRT) system that uses an X-ray linear accelerator gated to the motion of internal fiducial markers introduced in the late 1990s. Relying on more than 10 years of clinical experience and big log data, we established a real-time image gated proton beam therapy system dedicated to spot scanning. Using log data and clinical outcomes derived from the clinical usage of the RTRT system since 1999, we have established a library to be used for in-house simulation for tumor targeting and evaluation. Factors considered to be the dominant causes of the interplay effects related to the spot scanning dedicated proton therapy system are listed and discussed. Total facility design, synchrotron operation cycle, and gating windows were listed as the important factors causing the interplay effects contributing to the irradiation time and motion-induced dose error. Fiducial markers that we have developed and used for the RTRT in X-ray therapy were suggested to have the capacity to improve dose distribution. Accumulated internal motion data in the RTRT system enable us to improve the operation and function of a Spot-scanning proton beam therapy (SSPT) system. A real-time-image gated SSPT system can increase accuracy for treating moving tumors. The system will start clinical service in early 2014. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy

NASA Astrophysics Data System (ADS)

Hälg, R. A.; Besserer, J.; Boschung, M.; Mayer, S.; Lomax, A. J.; Schneider, U.

2014-05-01

In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy.

PubMed

Hälg, R A; Besserer, J; Boschung, M; Mayer, S; Lomax, A J; Schneider, U

2014-05-21

In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

Helium-3 and helium-4 acceleration by high power laser pulses for hadron therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bulanov, S. S.; Esarey, E.; Schroeder, C. B.

The laser driven acceleration of ions is considered a promising candidate for an ion source for hadron therapy of oncological diseases. Though proton and carbon ion sources are conventionally used for therapy, other light ions can also be utilized. Whereas carbon ions require 400 MeV per nucleon to reach the same penetration depth as 250 MeV protons, helium ions require only 250 MeV per nucleon, which is the lowest energy per nucleon among the light ions (heavier than protons). This fact along with the larger biological damage to cancer cells achieved by helium ions, than that by protons, makes thismore » species an interesting candidate for the laser driven ion source. Two mechanisms (magnetic vortex acceleration and hole-boring radiation pressure acceleration) of PW-class laser driven ion acceleration from liquid and gaseous helium targets are studied with the goal of producing 250 MeV per nucleon helium ion beams that meet the hadron therapy requirements. We show that He3 ions, having almost the same penetration depth as He4 with the same energy per nucleon, require less laser power to be accelerated to the required energy for the hadron therapy.« less

Helium-3 and helium-4 acceleration by high power laser pulses for hadron therapy

DOE PAGES

Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; ...

2015-06-24

The laser driven acceleration of ions is considered a promising candidate for an ion source for hadron therapy of oncological diseases. Though proton and carbon ion sources are conventionally used for therapy, other light ions can also be utilized. Whereas carbon ions require 400 MeV per nucleon to reach the same penetration depth as 250 MeV protons, helium ions require only 250 MeV per nucleon, which is the lowest energy per nucleon among the light ions (heavier than protons). This fact along with the larger biological damage to cancer cells achieved by helium ions, than that by protons, makes thismore » species an interesting candidate for the laser driven ion source. Two mechanisms (magnetic vortex acceleration and hole-boring radiation pressure acceleration) of PW-class laser driven ion acceleration from liquid and gaseous helium targets are studied with the goal of producing 250 MeV per nucleon helium ion beams that meet the hadron therapy requirements. We show that He3 ions, having almost the same penetration depth as He4 with the same energy per nucleon, require less laser power to be accelerated to the required energy for the hadron therapy.« less

A beam monitor based on MPGD detectors for hadron therapy

NASA Astrophysics Data System (ADS)

Altieri, P. R.; Di Benedetto, D.; Galetta, G.; Intonti, R. A.; Mercadante, A.; Nuzzo, S.; Verwilligen, P.

2018-02-01

Remarkable scientific and technological progress during the last years has led to the construction of accelerator based facilities dedicated to hadron therapy. This kind of technology requires precise and continuous control of position, intensity and shape of the ions or protons used to irradiate cancers. Patient safety, accelerator operation and dose delivery should be optimized by a real time monitoring of beam intensity and profile during the treatment, by using non-destructive, high spatial resolution detectors. In the framework of AMIDERHA (AMIDERHA - Enhanced Radiotherapy with HAdron) project funded by the Ministero dell'Istruzione, dell'Università e della Ricerca (Italian Ministry of Education and Research) the authors are studying and developing an innovative beam monitor based on Micro Pattern Gaseous Detectors (MPDGs) characterized by a high spatial resolution and rate capability. The Monte Carlo simulation of the beam monitor prototype was carried out to optimize the geometrical set up and to predict the behavior of the detector. A first prototype has been constructed and successfully tested using 55Fe, 90Sr and also an X-ray tube. Preliminary results on both simulations and tests will be presented.

MO-FG-CAMPUS-JeP1-03: Luminescence Imaging of Water During Proton Beam Irradiation for Range Estimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, S; Komori, M; Toshito, T

Purpose: Since proton therapy has the ability to selectively deliver a dose to a target tumor, the dose distribution should be accurately measured. A precise and efficient method to evaluate the dose distribution is desired. We found that luminescence was emitted from water during proton irradiation and thought this phenomenon could be used for estimating the dose distribution. Methods: For this purpose, we placed water phantoms set on a table with a spot-scanning proton-therapy system, and luminescence images of these phantoms were measured with a high-sensitivity cooled charge coupled device (CCD) camera during proton-beam irradiation. We also conducted the imagingmore » of phantoms of pure-water, fluorescein solution and acrylic block. We made three dimensional images from the projection data. Results: The luminescence images of water phantoms during the proton-beam irradiations showed clear Bragg peaks, and the measured proton ranges from the images were almost the same as those obtained with an ionization chamber. The image of the pure-water phantom also showed almost the same distribution as the tap-water phantom, indicating that the luminescence image was not related to impurities in the water. The luminescence image of fluorescein solution had ∼3 times higher intensity than water, with the same proton range as that of water. The luminescence image of the acrylic phantom had 14.5% shorter proton range than that of water; the proton range in the acrylic phantom was relatively matched with the calculated value. The luminescence images of the tap-water phantom during proton irradiation could be obtained in less than 2 sec. Three dimensional images were successfully obtained which have more quantitative information. Conclusion: Luminescence imaging during proton-beam irradiation has the potential to be a new method for range estimations in proton therapy.« less

Characterization of light transmissions in various optical fibers with proton beam

NASA Astrophysics Data System (ADS)

Song, Young Beom; Kim, Hye Jin; Kim, Mingeon; Lee, Bongsoo; Shin, Sang Hun; Yoo, Wook Jae; Jang, Kyoung Won; Hwang, Sung Won

2017-12-01

As a feasibility study on the development of a fiber-optic radiation sensor for proton therapy dosimetry, we characterized light transmissions of various commercial optical fibers such as silica and plastic based optical fibers by the irradiation of proton beams. In this study, we measured light transmission spectra of optical fibers as a function of absorbed doses of proton beams using a deuterium & tungsten halogen lamps and a spectrometer. To be used as a fiber-optic radiation sensor, the optical fibers should have the radiation resistant characteristics and provide stable output signals during the proton beam irradiation. In this study, we could select suitable optical fibers to be used in the fiber-optic radiation sensor without quenching effects for proton therapy dosimetry. As a result, the light transmittance of the optical fibers had decreasing trends with increasing absorbed dose as expected.

[Heavy charged particle radiotherapy--proton beam].

PubMed

Ogino, Takashi

2003-12-01

Proton beam therapy (PBT) makes it possible to deliver a higher concentration of radiation to the tumor by its Bragg-peak, and is easy to utilize due to its identical biological characteristics with X-rays. PBT has a half-century history, and more than 35,000 patients have been reported as having had treatments with proton beams worldwide. The historic change to this therapy occurred in the 1990s, when the Loma Linda University Medical Center began clinical activity as the first hospital in the world to utilize a medically dedicated proton therapy facility. Since then, similar hospital-based medically dedicated facilities have been constructed. Results from around the world have shown the therapeutic superiority of PBT over alternative treatment options for ocular melanoma, skull base sarcoma, head and neck cancer, lung cancer, esophageal cancer, hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve further advancement both clinically and technologically.

MICRODOSIMETRIC MEASUREMENT OF SECONDARY RADIATION IN THE PASSIVE SCATTERED PROTON THERAPY ROOM OF iTHEMBA LABS USING A TISSUE-EQUIVALENT PROPORTIONAL COUNTER.

PubMed

Chiriotti, S; Parisi, A; Vanhavere, F; De Saint-Hubert, M; Vandevoorde, C; Slabbert, J; Beukes, P; de Kock, E; Symons, J

2018-04-13

Measurements of the dose equivalent at different distances from the isocenter of the proton therapy center at iThemba LABS were previously performed with a tissue-equivalent proportional counter (TEPC). These measurements showed that the scattered radiation levels were one or two orders of magnitude higher in comparison to other passive scattering delivery systems. In order to reduce these radiation levels, additional shielding was installed shortly after the measurements were done. Therefore, the aim of this work is to quantify and assess the reduction of the secondary doses delivered in the proton therapy room at iThemba LABS after the installation of the additional shielding. This has been performed by measuring microdosimetric spectra with a TEPC at 11 locations around the isocenter when a clinical modulated beam of 200 MeV proton was impinging onto a water phantom placed at the isocenter.

Repetitive Pediatric Anesthesia in a Non-Hospital Setting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchsbaum, Jeffrey C., E-mail: jbuchsba@iupui.edu; Indiana University Health Proton Therapy Center, Bloomington, Indiana; McMullen, Kevin P.

2013-04-01

Purpose: Repetitive sedation/anesthesia (S/A) for children receiving fractionated radiation therapy requires induction and recovery daily for several weeks. In the vast majority of cases, this is accomplished in an academic center with direct access to pediatric faculty and facilities in case of an emergency. Proton radiation therapy centers are more frequently free-standing facilities at some distance from specialized pediatric care. This poses a potential dilemma in the case of children requiring anesthesia. Methods and Materials: The records of the Indiana University Health Proton Therapy Center were reviewed for patients requiring anesthesia during proton beam therapy (PBT) between June 1, 2008,more » and April 12, 2012. Results: A total of 138 children received daily anesthesia during this period. A median of 30 fractions (range, 1-49) was delivered over a median of 43 days (range, 1-74) for a total of 4045 sedation/anesthesia procedures. Three events (0.0074%) occurred, 1 fall from a gurney during anesthesia recovery and 2 aspiration events requiring emergency department evaluation. All 3 children did well. One aspiration patient needed admission to the hospital and mechanical ventilation support. The other patient returned the next day for treatment without issue. The patient who fell was not injured. No patient required cessation of therapy. Conclusions: This is the largest reported series of repetitive pediatric anesthesia in radiation therapy, and the only available data from the proton environment. Strict adherence to rigorous protocols and a well-trained team can safely deliver daily sedation/anesthesia in free-standing proton centers.« less

Future Directions in Medical Physics

NASA Astrophysics Data System (ADS)

Jeraj, Robert

Medical Physics is a highly interdisciplinary field at the intersection between physics and medicine and biology. Medical Physics is aiming at development of novel applications of physical processes and techniques in various areas of medicine and biology. Medical Physics had and continues to have profound impact by developing improved imaging and treatment technologies, and helping to advance our understanding of the complexity of the disease. The general trend in medicine towards personalized therapy, and emphasis on accelerated translational research is having a profound impact on medical physics as well. In the traditional stronghold for medical physicists - radiation therapy - the new reality is shaping in the form of biologically conformal and combination therapies, as well as advanced particle therapy approaches, such as proton and ion therapies. Rapid increase in faster and more informative multi-modality medical imaging is bringing a wealth of information that is being complemented with data obtained from genomic profiling and other biomarkers. Novel data analysis and data mining approaches are proving grounds for employment of various artificial intelligence methods that will help further improving clinical decision making for optimization of various therapies as well as better understanding of the disease properties and disease evolution, ultimately leading to improved clinical outcomes.

Operation of the Preclinical Head Scanner for Proton CT.

PubMed

Sadrozinski, H F-W; Geoghegan, T; Harvey, E; Johnson, R P; Plautz, T E; Zatserklyaniy, A; Bashkirov, V; Hurley, R F; Piersimoni, P; Schulte, R W; Karbasi, P; Schubert, K E; Schultze, B; Giacometti, V

2016-09-21

We report on the operation and performance tests of a preclinical head scanner developed for proton computed tomography (pCT). After extensive preclinical testing, pCT is intended to be employed in support of proton therapy treatment planning and pre-treatment verification in patients undergoing particle-beam therapy. In order to assess the performance of the scanner, we have performed CT scans with 200 MeV protons from both the synchrotron of the Loma Linda University Medical Center (LLUMC) and the cyclotron of the Northwestern Medicine Chicago Proton Center (NMCPC). The very high sustained rate of data acquisition, exceeding one million protons per second, allowed a full 360° scan to be completed in less than 7 minutes. The reconstruction of various phantoms verified accurate reconstruction of the proton relative stopping power (RSP) and the spatial resolution in a variety of materials. The dose for an image with better than 1% uncertainty in the RSP is found to be close to 1 mGy.

In vivo proton range verification: a review

NASA Astrophysics Data System (ADS)

Knopf, Antje-Christin; Lomax, Antony

2013-08-01

Protons are an interesting modality for radiotherapy because of their well defined range and favourable depth dose characteristics. On the other hand, these same characteristics lead to added uncertainties in their delivery. This is particularly the case at the distal end of proton dose distributions, where the dose gradient can be extremely steep. In practice however, this gradient is rarely used to spare critical normal tissues due to such worries about its exact position in the patient. Reasons for this uncertainty are inaccuracies and non-uniqueness of the calibration from CT Hounsfield units to proton stopping powers, imaging artefacts (e.g. due to metal implants) and anatomical changes of the patient during treatment. In order to improve the precision of proton therapy therefore, it would be extremely desirable to verify proton range in vivo, either prior to, during, or after therapy. In this review, we describe and compare state-of-the art in vivo proton range verification methods currently being proposed, developed or clinically implemented.

Proton beam therapy and the convoluted pathway to incorporating emerging technology into routine medical care in the United States.

PubMed

Steinberg, Michael L; Konski, Andre

2009-01-01

The pathway that emerging medical technologies take to incorporation into routine medical care in the United States is a product of the social, economic, and political milieu. Our review explores how this milieu brought the incorporation of proton beam therapy into the healthcare delivery system to its current point. We look at how new technologies are presently accepted into this system and discuss the emerging trends--such as the use of evidence-based assessment of technology, coverage with evidence policies, and comparative effectiveness analysis--that are affecting proton beam therapy's effort to finds its place in the pantheon of available medical treatments for patients with cancer.

Design and application of 3D-printed stepless beam modulators in proton therapy

NASA Astrophysics Data System (ADS)

Lindsay, C.; Kumlin, J.; Martinez, D. M.; Jirasek, A.; Hoehr, C.

2016-06-01

A new method for the design of stepless beam modulators for proton therapy is described and verified. Simulations of the classic designs are compared against the stepless method for various modulation widths which are clinically applicable in proton eye therapy. Three modulator wheels were printed using a Stratasys Objet30 3D printer. The resulting depth dose distributions showed improved uniformity over the classic stepped designs. Simulated results imply a possible improvement in distal penumbra width; however, more accurate measurements are needed to fully verify this effect. Lastly, simulations were done to model bio-equivalence to Co-60 cell kill. A wheel was successfully designed to flatten this metric.

Beam shaping assembly design of 7Li(p,n)7Be neutron source for boron neutron capture therapy of deep-seated tumor.

PubMed

Zaidi, L; Belgaid, M; Taskaev, S; Khelifi, R

2018-05-31

The development of a medical facility for boron neutron capture therapy at Budker Institute of Nuclear Physics is under way. The neutron source is based on a tandem accelerator with vacuum insulation and lithium target. The proposed accelerator is conceived to deliver a proton beam around 10 mA at 2.3 MeV proton beam. To deliver a therapeutic beam for treatment of deep-seated tumors a typical Beam Shaping Assembly (BSA) based on the source specifications has been explored. In this article, an optimized BSA based on the 7 Li(p,n) 7 Be neutron production reaction is proposed. To evaluate the performance of the designed beam in a phantom, the parameters and the dose profiles in tissues due to the irradiation have been considered. In the simulations, we considered a proton energy of 2.3 MeV, a current of 10 mA, and boron concentrations in tumor, healthy tissues and skin of 52.5 ppm, 15 ppm and 22.5 ppm, respectively. It is found that, for a maximum punctual healthy tissue dose seated to 11 RBE-Gy, a mean dose of 56.5 RBE Gy with a minimum of 52.2 RBE Gy can be delivered to a tumor in 40 min, where the therapeutic ratio is estimated to 5.38. All of these calculations were carried out using the Monte Carlo MCNP code. Copyright © 2018 Elsevier Ltd. All rights reserved.

TU-G-BRB-03: IROC Houston’s Proton Beam Validation for Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, P.

2015-06-15

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. Themore » lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle clinical trial development and support. Research reported in this presentation is supported by the National Cancer Institute of the National; Institutes of Health under Award Number P20CA183640.« less

SU-F-T-205: Effectiveness of Robust Treatment Planning to Account for Inter- Fractional Variation in Intensity Modulated Proton Therapy for Head Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, X; Zhang, J; Qin, A

2016-06-15

Purpose: To evaluate the potential benefits of robust optimization in intensity modulated proton therapy(IMPT) treatment planning to account for inter-fractional variation for Head Neck Cancer(HNC). Methods: One patient with bilateral HNC previous treated at our institution was used in this study. Ten daily CBCTs were selected. The CT numbers of the CBCTs were corrected by mapping the CT numbers from simulation CT via Deformable Image Registration. The planning target volumes(PTVs) were defined by a 3mm expansion from clinical target volumes(CTVs). The prescription was 70Gy, 54Gy to CTV1, CTV2, and PTV1, PTV2 for robust optimized(RO) and conventionally optimized(CO) plans respectively. Bothmore » techniques were generated by RayStation with the same beam angles: two anterior oblique and two posterior oblique angles. The similar dose constraints were used to achieve 99% of CTV1 received 100% prescription dose while kept the hotspots less than 110% of the prescription. In order to evaluate the dosimetric result through the course of treatment, the contours were deformed from simulation CT to daily CBCTs, modified, and approved by a radiation oncologist. The initial plan on the simulation CT was re-replayed on the daily CBCTs followed the bony alignment. The target coverage was evaluated using the daily doses and the cumulative dose. Results: Eight of 10 daily deliveries with using RO plan achieved at least 95% prescription dose to CTV1 and CTV2, while still kept maximum hotspot less than 112% of prescription compared with only one of 10 for the CO plan to achieve the same standards. For the cumulative doses, the target coverage for both RO and CO plans was quite similar, which was due to the compensation of cold and hot spots. Conclusion: Robust optimization can be effectively applied to compensate for target dose deficit caused by inter-fractional target geometric variation in IMPT treatment planning.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, N

Purpose: Ocular proton therapy has the following advantages: i) sparing optic nerve, ii) the minimal dose is delivered to surrounding normal tissues. Since the proton therapy center was opened in 2007, 30 patients with ocular tumor have been treated at National Cancer Center using single scattering technique. To develop a solid eye phantom which can verify the output and the beam range with EBT3 film for independent patient QA in ocular proton therapy. Methods: The proton therapy is very effective to treat ocular tumor, because of the Bragg peak feature. In general, the beam shape of eye treatment is aboutmore » 3 cm in diameter and the beam range is under 5 cm. However, proton therapy has uncertainty of beam range problem due to various stopping power of normal tissue, bone, air and so on, so that we should verify the beam range before treatment. For this purpose, a new PMMA phantom with wedge has been developed to use the film dosimetry and the ionization chamber. It is able to place a film on the slope of the phantom, which the spread out Bragg Peak by the water equivalent thickness value of PMMA can be made on the film. We considered to relation with quenching effect of proton energy and range for simple second check. In addition, the ionization chamber (Pin-point chamber, PTW 31014) can be inserted into a hole in the phantom to measure the absolute dose. Results: The output difference and beam range difference were less than 2% and 1.0 mm, respectively, between the measurement and the plan. Conclusion: An eye phantom was developed and its performance was evaluated successfully and it was useful to verify the output. Also with EBT3 film with the quenching effect for measurement depth-dose profile, range to patient QA.« less

Characteristics of fiber-optic radiation sensor for passive scattering proton beams

NASA Astrophysics Data System (ADS)

Son, J.; Kim, M.; Jeong, J.; Lim, Y.; Lee, S. B.; Shin, D.; Yoon, M.

2017-11-01

The aims of this study were to investigate the characteristics of a fiber-optic radiation sensor (FORS) that detects the fluorescence light produced by proton beam and to verify its effectiveness in proton therapy quality assurance (QA). Various characteristics of the FORS were investigated, such as the linearity of its relationships to the sensitive length of fiber for the proton beams of intermediate ranges (165.46 and 178.37 MeV) and to the measured dose, as well as its dose rate dependence. In addition, patient specific precription dose QA was conducted for five patients actually undergoing proton therapy and the results were compared with the doses measured using an ion chamber. The results show that the signal of the FORS is linearly related to the sensitive length of fiber and to the irradiated dose in the range from 1 to 500 cGy. The QA results obtained using the FORS system showed good agreement with the corresponding ion chamber results, with an average difference of 0.40% and a standard deviation of 0.35%. The FORS was dose-rate independent for proton currents up to 5 Gy/min. The profiles of various proton beams obtained using an array of FORS, which were measured as an application of the developed dosimetric system, closely agreed with the profiles acquired using EBT3 film. In summary, the experimental results of FORS demonstrated its effectiveness for use in various proton therapy QA tests.

Benchmarking of a treatment planning system for spot scanning proton therapy: Comparison and analysis of robustness to setup errors of photon IMRT and proton SFUD treatment plans of base of skull meningioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harding, R., E-mail: ruth.harding2@wales.nhs.uk; Trnková, P.; Lomax, A. J.

Purpose: Base of skull meningioma can be treated with both intensity modulated radiation therapy (IMRT) and spot scanned proton therapy (PT). One of the main benefits of PT is better sparing of organs at risk, but due to the physical and dosimetric characteristics of protons, spot scanned PT can be more sensitive to the uncertainties encountered in the treatment process compared with photon treatment. Therefore, robustness analysis should be part of a comprehensive comparison between these two treatment methods in order to quantify and understand the sensitivity of the treatment techniques to uncertainties. The aim of this work was tomore » benchmark a spot scanning treatment planning system for planning of base of skull meningioma and to compare the created plans and analyze their robustness to setup errors against the IMRT technique. Methods: Plans were produced for three base of skull meningioma cases: IMRT planned with a commercial TPS [Monaco (Elekta AB, Sweden)]; single field uniform dose (SFUD) spot scanning PT produced with an in-house TPS (PSI-plan); and SFUD spot scanning PT plan created with a commercial TPS [XiO (Elekta AB, Sweden)]. A tool for evaluating robustness to random setup errors was created and, for each plan, both a dosimetric evaluation and a robustness analysis to setup errors were performed. Results: It was possible to create clinically acceptable treatment plans for spot scanning proton therapy of meningioma with a commercially available TPS. However, since each treatment planning system uses different methods, this comparison showed different dosimetric results as well as different sensitivities to setup uncertainties. The results confirmed the necessity of an analysis tool for assessing plan robustness to provide a fair comparison of photon and proton plans. Conclusions: Robustness analysis is a critical part of plan evaluation when comparing IMRT plans with spot scanned proton therapy plans.« less

WE-E-BRB-02: Implementation of Pencil Beam Scanning (PBS) Proton Therapy Treatment for Liver Patient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, L.

Strategies for treating thoracic and liver tumors using pencil beam scanning proton therapy Thoracic and liver tumors have not been treated with pencil beam scanning (PBS) proton therapy until recently. This is because of concerns about the significant interplay effects between proton spot scanning and patient’s respiratory motion. However, not all tumors have unacceptable magnitude of motion for PBS proton therapy. Therefore it is important to analyze the motion and understand the significance of the interplay effect for each patient. The factors that affect interplay effect and its washout include magnitude of motion, spot size, spot scanning sequence and speed.more » Selection of beam angle, scanning direction, repainting and fractionation can all reduce the interplay effect. An overview of respiratory motion management in PBS proton therapy including assessment of tumor motion and WET evaluation will be first presented. As thoracic tumors have very different motion patterns from liver tumors, examples would be provided for both anatomic sites. As thoracic tumors are typically located within highly heterogeneous environments, dose calculation accuracy is a concern for both treatment target and surrounding organs such as spinal cord or esophagus. Strategies for mitigating the interplay effect in PBS will be presented and the pros and cons of various motion mitigation strategies will be discussed. Learning Objectives: Motion analysis for individual patients with respect to interplay effect Interplay effect and mitigation strategies for treating thoracic/liver tumors with PBS Treatment planning margins for PBS The impact of proton dose calculation engines over heterogeneous treatment target and surrounding organs I have a current research funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian; L. Lin, I have a current funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian.; H. Li, Na.« less

WE-E-BRB-01: Personalized Motion Management Strategies for Pencil Beam Scanning Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, X.

Strategies for treating thoracic and liver tumors using pencil beam scanning proton therapy Thoracic and liver tumors have not been treated with pencil beam scanning (PBS) proton therapy until recently. This is because of concerns about the significant interplay effects between proton spot scanning and patient’s respiratory motion. However, not all tumors have unacceptable magnitude of motion for PBS proton therapy. Therefore it is important to analyze the motion and understand the significance of the interplay effect for each patient. The factors that affect interplay effect and its washout include magnitude of motion, spot size, spot scanning sequence and speed.more » Selection of beam angle, scanning direction, repainting and fractionation can all reduce the interplay effect. An overview of respiratory motion management in PBS proton therapy including assessment of tumor motion and WET evaluation will be first presented. As thoracic tumors have very different motion patterns from liver tumors, examples would be provided for both anatomic sites. As thoracic tumors are typically located within highly heterogeneous environments, dose calculation accuracy is a concern for both treatment target and surrounding organs such as spinal cord or esophagus. Strategies for mitigating the interplay effect in PBS will be presented and the pros and cons of various motion mitigation strategies will be discussed. Learning Objectives: Motion analysis for individual patients with respect to interplay effect Interplay effect and mitigation strategies for treating thoracic/liver tumors with PBS Treatment planning margins for PBS The impact of proton dose calculation engines over heterogeneous treatment target and surrounding organs I have a current research funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian; L. Lin, I have a current funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian.; H. Li, Na.« less

WE-E-BRB-00: Motion Management for Pencil Beam Scanning Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Strategies for treating thoracic and liver tumors using pencil beam scanning proton therapy Thoracic and liver tumors have not been treated with pencil beam scanning (PBS) proton therapy until recently. This is because of concerns about the significant interplay effects between proton spot scanning and patient’s respiratory motion. However, not all tumors have unacceptable magnitude of motion for PBS proton therapy. Therefore it is important to analyze the motion and understand the significance of the interplay effect for each patient. The factors that affect interplay effect and its washout include magnitude of motion, spot size, spot scanning sequence and speed.more » Selection of beam angle, scanning direction, repainting and fractionation can all reduce the interplay effect. An overview of respiratory motion management in PBS proton therapy including assessment of tumor motion and WET evaluation will be first presented. As thoracic tumors have very different motion patterns from liver tumors, examples would be provided for both anatomic sites. As thoracic tumors are typically located within highly heterogeneous environments, dose calculation accuracy is a concern for both treatment target and surrounding organs such as spinal cord or esophagus. Strategies for mitigating the interplay effect in PBS will be presented and the pros and cons of various motion mitigation strategies will be discussed. Learning Objectives: Motion analysis for individual patients with respect to interplay effect Interplay effect and mitigation strategies for treating thoracic/liver tumors with PBS Treatment planning margins for PBS The impact of proton dose calculation engines over heterogeneous treatment target and surrounding organs I have a current research funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian; L. Lin, I have a current funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian.; H. Li, Na.« less

WE-E-BRB-03: Implementation of PBS Proton Therapy Treatment for Free Breathing Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, H.

Strategies for treating thoracic and liver tumors using pencil beam scanning proton therapy Thoracic and liver tumors have not been treated with pencil beam scanning (PBS) proton therapy until recently. This is because of concerns about the significant interplay effects between proton spot scanning and patient’s respiratory motion. However, not all tumors have unacceptable magnitude of motion for PBS proton therapy. Therefore it is important to analyze the motion and understand the significance of the interplay effect for each patient. The factors that affect interplay effect and its washout include magnitude of motion, spot size, spot scanning sequence and speed.more » Selection of beam angle, scanning direction, repainting and fractionation can all reduce the interplay effect. An overview of respiratory motion management in PBS proton therapy including assessment of tumor motion and WET evaluation will be first presented. As thoracic tumors have very different motion patterns from liver tumors, examples would be provided for both anatomic sites. As thoracic tumors are typically located within highly heterogeneous environments, dose calculation accuracy is a concern for both treatment target and surrounding organs such as spinal cord or esophagus. Strategies for mitigating the interplay effect in PBS will be presented and the pros and cons of various motion mitigation strategies will be discussed. Learning Objectives: Motion analysis for individual patients with respect to interplay effect Interplay effect and mitigation strategies for treating thoracic/liver tumors with PBS Treatment planning margins for PBS The impact of proton dose calculation engines over heterogeneous treatment target and surrounding organs I have a current research funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian; L. Lin, I have a current funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian.; H. Li, Na.« less

SU-E-J-213: Imaging and Treatment Isocenter Verification of a Gantry Mounted Proton Therapy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, S; Goddu, S; Rankine, L

2014-06-01

Purpose: The Mevion proton therapy machine is the first to feature a gantry mounted sychro-cyclotron. In addition, the system utilizes a 6D motion couch and kV imaging for precise proton therapy. To quantify coincidence between these systems, isocentricity tests were performed based on kV imaging alignment using radiochromic film. Methods: The 100 ton gantry and 6D robotic couch can rotate 190° around isocenter to provide necessary beam angles for treatment. The kV sources and detector panels are deployed as needed to acquire orthogonal portals. Gantry and couch mechanical isocenter were tested using star-shots and radiochromic-film (RCF). Using kV imaging, themore » star-shot phantom was aligned to an embedded fiducial and the isocenter was marked on RCF with a pinprick. The couch and gantry stars were performed by irradiating films at every 45° and 30°, respectively. A proton beam with a range and modulation-width of 18 cm was used. A Winston-Lutz test was also performed at the same gantry and couch rotations using a custom jig holding RCF and a tungsten ball placed at isocenter. A 2 cm diameter circular aperture was used for the irradiation. Results: The couch star-shot indicated a minimum tangent circle of 0.6 mm, with a 0.9 mm offset from the manually marked isocenter. The gantry star-shot showed a 0.6 mm minimum tangent circle with a 0.5 mm offset from the pinprick. The Winston Lutz test performed for gantry rotation showed a maximum deviation from center of 0.5 mm. Conclusion: Based on star-shots and Winston-Lutz tests, the proton gantry and 6D couch isocentricity are within 1 mm. In this study, we have shown that the methods commonly utilized for Linac characterization can be applied to proton therapy. This revolutionary proton therapy system possesses excellent agreement between the mechanical and radiation isocenter, providing highly precise treatment.« less

Evaluating analytical ionization quenching correction models for 3D liquid organic scintillator detector

NASA Astrophysics Data System (ADS)

Alsanea, F.; Beddar, S.

2017-05-01

Proton therapy offers dosimetric advantage over conventional photon therapy due to the finite range of the proton beam, which improves dose conformity. However, one of the main challenges of proton beam therapy is verification of the complex treatment plans delivered to a patient. Thus, 3D measurements are needed to verify the complex dose distribution. A 3D organic scintillator detector is capable of such measurements. However, organic scintillators exhibit a non-linear relation to the ionization density called ionization quenching. The ionization quenching phenomenon in organic scintillators must be accounted for to obtain accurate dose measurements. We investigated the energy deposition by secondary electrons (EDSE) model to explain ionization quenching in 3D liquid organic scintillator when exposed to proton beams. The EDSE model was applied to volumetric scintillation measurement of proton pencil beam with energies of 85.6, 100.9, 144.9 and 161.9 MeV. The quenching parameter in EDSE model ρq was determined by plotting the total light output vs the initial energy of the ion. The results were compared to the Birks semi-empirical formula of scintillation light emission.

Impact of Real-Time Image Gating on Spot Scanning Proton Therapy for Lung Tumors: A Simulation Study.

PubMed

Kanehira, Takahiro; Matsuura, Taeko; Takao, Seishin; Matsuzaki, Yuka; Fujii, Yusuke; Fujii, Takaaki; Ito, Yoichi M; Miyamoto, Naoki; Inoue, Tetsuya; Katoh, Norio; Shimizu, Shinichi; Umegaki, Kikuo; Shirato, Hiroki

2017-01-01

To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW). A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of ±1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy. The prescribed dose was 70 Gy (relative biological effectiveness)/10 fractions to 99% of the target. Each of the 3-dimensional marker positions in the time series was associated with the appropriate 4-dimensional computed tomography phase. The 4-dimensional dose calculations were performed. The dose distribution in each respiratory phase was deformed into the end-exhale computed tomography image. The D99 and D5 to D95 of the clinical target volume scaled by the prescribed dose with criteria of D99 >95% and D5 to D95 <5%, V20 for the normal lung, and treatment times were evaluated. Gating windows ≤ ±2 mm fulfilled the CTV criteria for all patients (whereas the criteria were not always met for GWs ≥ ±3 mm) and gave an average reduction in V20 of more than 17.2% relative to free-breathing proton therapy (whereas GWs ≥ ±4 mm resulted in similar or increased V20). The average (maximum) irradiation times were 384 seconds (818 seconds) for the ±1-mm GW, but less than 226 seconds (292 seconds) for the ±2-mm GW. The maximum increased considerably at ±1-mm GW. Real-time-image gated proton beam therapy with a GW of ±2 mm was demonstrated to be suitable, providing good dose distribution without greatly extending treatment time. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Real-Time Image Gating on Spot Scanning Proton Therapy for Lung Tumors: A Simulation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanehira, Takahiro; Matsuura, Taeko, E-mail: matsuura@med.hokudai.ac.jp; Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo

Purpose: To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW). Methods and Materials: A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of ±1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy. The prescribed dose was 70 Gy (relative biological effectiveness)/10 fractions to 99% of the target. Each of the 3-dimensional marker positions in themore » time series was associated with the appropriate 4-dimensional computed tomography phase. The 4-dimensional dose calculations were performed. The dose distribution in each respiratory phase was deformed into the end-exhale computed tomography image. The D99 and D5 to D95 of the clinical target volume scaled by the prescribed dose with criteria of D99 >95% and D5 to D95 <5%, V20 for the normal lung, and treatment times were evaluated. Results: Gating windows ≤ ±2 mm fulfilled the CTV criteria for all patients (whereas the criteria were not always met for GWs ≥ ±3 mm) and gave an average reduction in V20 of more than 17.2% relative to free-breathing proton therapy (whereas GWs ≥ ±4 mm resulted in similar or increased V20). The average (maximum) irradiation times were 384 seconds (818 seconds) for the ±1-mm GW, but less than 226 seconds (292 seconds) for the ±2-mm GW. The maximum increased considerably at ±1-mm GW. Conclusion: Real-time-image gated proton beam therapy with a GW of ±2 mm was demonstrated to be suitable, providing good dose distribution without greatly extending treatment time.« less

Assessment of potential advantages of relevant ions for particle therapy: a model based study.

PubMed

Grün, Rebecca; Friedrich, Thomas; Krämer, Michael; Zink, Klemens; Durante, Marco; Engenhart-Cabillic, Rita; Scholz, Michael

2015-02-01

Different ion types offer different physical and biological advantages for therapeutic applications. The purpose of this work is to assess the advantages of the most commonly used ions in particle therapy, i.e., carbon ((12)C), helium ((4)He), and protons ((1)H) for different treatment scenarios. A treatment planning analysis based on idealized target geometries was performed using the treatment planning software TRiP98. For the prediction of the relative biological effectiveness (RBE) that is required for biological optimization in treatment planning the local effect model (LEM IV) was used. To compare the three ion types, the peak-to-entrance ratio (PER) was determined for the physical dose (PERPHY S), the RBE (PERRBE), and the RBE-weighted dose (PERBIO) resulting for different dose-levels, field configurations, and tissue types. Further, the dose contribution to artificial organs at risk (OAR) was assessed and a comparison of the dose distribution for the different ion types was performed for a patient with chordoma of the skull base. The study showed that the advantages of the ions depend on the physical and biological properties and the interplay of both. In the case of protons, the consideration of a variable RBE instead of the clinically applied generic RBE of 1.1 indicates an advantage in terms of an increased PERRBE for the analyzed configurations. Due to the fact that protons show a somewhat better PERPHY S compared to helium and carbon ions whereas helium shows a higher PERRBE compared to protons, both protons and helium ions show a similar RBE-weighted dose distribution. Carbon ions show the largest variation of the PERRBE with tissue type and a benefit for radioresistant tumor types due to their higher LET. Furthermore, in the case of a two-field irradiation, an additional gain in terms of PERBIO is observed when using an orthogonal field configuration for carbon ions as compared to opposing fields. In contrast, for protons, the PERBIO is almost independent on the field configuration. Concerning the artificial lateral OAR, the volume receiving 20% of the prescribed RBE-weighted dose (V20) was reduced by over 35% using helium ions and by over 40% using carbon ions compared to protons. The analysis of the patient plan showed that protons, helium, and carbon ions are similar in terms of target coverage whereas the dose to the surrounding tissue is increasing from carbon ions toward protons. The mean dose to the brain stem can be reduced by more than 55% when using helium ions and by further 25% when using carbon ions instead of protons. The comparison of the PERRBE and PERPHY S of the three ion types suggests a strong dependence of the advantages of the three ions on the dose-level, tissue type, and field configuration. In terms of conformity, i.e., dose to the normal tissue, a clear gain is expected using carbon or helium ions compared to protons.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohta, Kengo, E-mail: yesterday.is.yesterday@gmail.com; Shimohira, Masashi, E-mail: mshimohira@gmail.com; Sasaki, Shigeru, E-mail: ssasaki916@yahoo.co.jp

PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success ratesmore » of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.« less

Treatment of Helicobacter pylori infection: Current status and future concepts

PubMed Central

Yang, Jyh-Chin; Lu, Chien-Wei; Lin, Chun-Jung

2014-01-01

Helicobacter pylori (H. pylori) infection is highly associated with the occurrence of gastrointestinal diseases, including gastric inflammation, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid-tissue lymphoma. Although alternative therapies, including phytomedicines and probiotics, have been used to improve eradication, current treatment still relies on a combination of antimicrobial agents, such as amoxicillin, clarithromycin, metronidazole, and levofloxacin, and antisecretory agents, such as proton pump inhibitors (PPIs). A standard triple therapy consisting of a PPI and two antibiotics (clarithromycin and amoxicillin/metronidazole) is widely used as the first-line regimen for treatment of infection, but the increased resistance of H. pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy. Alternatively, levofloxacin-based triple therapy can be used as rescue therapy for H. pylori infection after failure of first-line therapy. The increase in resistance to antibiotics, including levofloxacin, may limit the applicability of such regimens. However, since resistance of H. pylori to amoxicillin is generally low, an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy. In addition, the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H. pylori infection, though its efficacy needs to be verified in clinical studies. PMID:24833858

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, M; Pompos, A; Gu, X

Purpose: To characterize the dose distributions of Cyberknife and intensity-modulated-proton-therapy (IMPT). Methods: A total of 20 patients previously treated with Cyberknife were selected. The original planning-target-volume (PTV) was used in the ‘IMPT-ideal’ plan assuming a comparable image-guidance with Cyberknife. A 3mm expansion was made to create the proton-PTV for the ‘IMPT-3mm’ plan representing the current proton-therapy where a margin of 3mm is used to account for the inferior image-guidance. The proton range uncertainty was taken-care in beam-design by adding the proximal- and distal-margins (3%water-equivalent-depth+1mm) for both proton plans. The IMPT plans were generated to meet the same target coverage asmore » the Cyberknife-plans. The plan quality of IMPT-ideal and IMPT-3mm were compared to the Cyberknife-plan. To characterize plan quality, we defined the ratio(R) of volumes encompassed by the selected isodose surfaces for Cyberknife and IMPT plans (VCK/VIMPT). Comparisons were made for both Cyberknife versus IMPT-ideal and Cyberknife versusIMPT-3mm to further discuss the impact of setup error margins used in proton therapy and the correlation with target size and location. Results: IMPT-ideal plans yield comparable plan quality as CK plans and slightly better OAR sparing while the IMPT-3mm plan results in a higher dose to the OARs, especially for centralized tumors. Comparing to the IMPT-ideal plans, a slightly larger 80% (Ravg=1.05) dose cloud and significantly larger 50% (Ravg=1.3) and 20% (Ravg=1.60) dose clouds are seen in CK plans. However, the 3mm expansion results in a larger high and medium dose clouds in IMPT-3mm plans (Ravg=0.65 for 80%-isodose; Ravg=0.93 for 50%-isodose). The trend increases with the size of the target and the distance from the brainstem to the center of target. Conclusion: Cyberknife is more preferable for treating centralized targets and proton therapy is advantageous for the large and peripheral targets. Advanced image guidance would improve the efficacy of proton therapy for intracranial treatments.« less

Commissioning an in-room mobile CT for adaptive proton therapy with a compact proton system.

PubMed

Oliver, Jasmine A; Zeidan, Omar; Meeks, Sanford L; Shah, Amish P; Pukala, Jason; Kelly, Patrick; Ramakrishna, Naren R; Willoughby, Twyla R

2018-05-01

To describe the commissioning of AIRO mobile CT system (AIRO) for adaptive proton therapy on a compact double scattering proton therapy system. A Gammex phantom was scanned with varying plug patterns, table heights, and mAs on a CT simulator (CT Sim) and on the AIRO. AIRO-specific CT-stopping power ratio (SPR) curves were created with a commonly used stoichiometric method using the Gammex phantom. A RANDO anthropomorphic thorax, pelvis, and head phantom, and a CIRS thorax and head phantom were scanned on the CT Sim and AIRO. Clinically realistic treatment plans and nonclinical plans were generated on the CT Sim images and subsequently copied onto the AIRO CT scans for dose recalculation and comparison for various AIRO SPR curves. Gamma analysis was used to evaluate dosimetric deviation between both plans. AIRO CT values skewed toward solid water when plugs were scanned surrounded by other plugs in phantom. Low-density materials demonstrated largest differences. Dose calculated on AIRO CT scans with stoichiometric-based SPR curves produced over-ranged proton beams when large volumes of low-density material were in the path of the beam. To create equivalent dose distributions on both data sets, the AIRO SPR curve's low-density data points were iteratively adjusted to yield better proton beam range agreement based on isodose lines. Comparison of the stoichiometric-based AIRO SPR curve and the "dose-adjusted" SPR curve showed slight improvement on gamma analysis between the treatment plan and the AIRO plan for single-field plans at the 1%, 1 mm level, but did not affect clinical plans indicating that HU number differences between the CT Sim and AIRO did not affect dose calculations for robust clinical beam arrangements. Based on this study, we believe the AIRO can be used offline for adaptive proton therapy on a compact double scattering proton therapy system. © 2018 Orlando Health UF Health Cancer Center. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

SU-E-T-628: Predicted Risk of Post-Irradiation Cerebral Necrosis in Pediatric Brain Cancer Patients: A Treatment Planning Comparison of Proton Vs. Photon Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freund, D; Zhang, R; Sanders, M

Purpose: Post-irradiation cerebral necrosis (PICN) is a severe late effect that can Result from brain cancers treatment using radiation therapy. The purpose of this study was to compare the treatment plans and predicted risk of PICN after volumetric modulated arc therapy (VMAT) to the risk after passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT) in a cohort of pediatric patients. Methods: Thirteen pediatric patients with varying age and sex were selected for this study. A clinical treatment volume (CTV) was constructed for 8 glioma patients and 5 ependymoma patients. Prescribed dose was 54 Gy over 30 fractionsmore » to the planning volume. Dosimetric endpoints were compared between VMAT and proton plans. The normal tissue complication probability (NTCP) following VMAT and proton therapy planning was also calculated using PICN as the biological endpoint. Sensitivity tests were performed to determine if predicted risk of PICN was sensitive to positional errors, proton range errors and selection of risk models. Results: Both PSPT and IMPT plans resulted in a significant increase in the maximum dose and reduction in the total brain volume irradiated to low doses compared with the VMAT plans. The average ratios of NTCP between PSPT and VMAT were 0.56 and 0.38 for glioma and ependymoma patients respectively and the average ratios of NTCP between IMPT and VMAT were 0.67 and 0.68 for glioma and ependymoma plans respectively. Sensitivity test revealed that predicted ratios of risk were insensitive to range and positional errors but varied with risk model selection. Conclusion: Both PSPT and IMPT plans resulted in a decrease in the predictive risk of necrosis for the pediatric plans studied in this work. Sensitivity analysis upheld the qualitative findings of the risk models used in this study, however more accurate models that take into account dose and volume are needed.« less

Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?

PubMed Central

Patel, S.; Kostaras, X.; Parliament, M.; Olivotto, I.A.; Nordal, R.; Aronyk, K.; Hagen, N.

2014-01-01

Background Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. Methods The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. Results Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. Summary Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases. PMID:25302033

Comparing the dosimetric impact of interfractional anatomical changes in photon, proton and carbon ion radiotherapy for pancreatic cancer patients

NASA Astrophysics Data System (ADS)

Houweling, Antonetta C.; Crama, Koen; Visser, Jorrit; Fukata, Kyohei; Rasch, Coen R. N.; Ohno, Tatsuya; Bel, Arjan; van der Horst, Astrid

2017-04-01

Radiotherapy using charged particles is characterized by a low dose to the surrounding healthy organs, while delivering a high dose to the tumor. However, interfractional anatomical changes can greatly affect the robustness of particle therapy. Therefore, we compared the dosimetric impact of interfractional anatomical changes (i.e. body contour differences and gastrointestinal gas volume changes) in photon, proton and carbon ion therapy for pancreatic cancer patients. In this retrospective planning study, photon, proton and carbon ion treatment plans were created for 9 patients. Fraction dose calculations were performed using daily cone-beam CT (CBCT) images. To this end, the planning CT was deformably registered to each CBCT; gastrointestinal gas volumes were delineated on the CBCTs and copied to the deformed CT. Fraction doses were accumulated rigidly. To compare planned and accumulated dose, dose-volume histogram (DVH) parameters of the planned and accumulated dose of the different radiotherapy modalities were determined for the internal gross tumor volume, internal clinical target volume (iCTV) and organs-at-risk (OARs; duodenum, stomach, kidneys, liver and spinal cord). Photon plans were highly robust against interfractional anatomical changes. The difference between the planned and accumulated DVH parameters for the photon plans was less than 0.5% for the target and OARs. In both proton and carbon ion therapy, however, coverage of the iCTV was considerably reduced for the accumulated dose compared with the planned dose. The near-minimum dose ({{D}98 % } ) of the iCTV reduced with 8% for proton therapy and with 10% for carbon ion therapy. The DVH parameters of the OARs differed less than 3% for both particle modalities. Fractionated radiotherapy using photons is highly robust against interfractional anatomical changes. In proton and carbon ion therapy, such changes can severely reduce the dose coverage of the target.

SU-E-J-143: Short- and Near-Term Effects of Proton Therapy On Cerebral White Matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uh, J; Merchant, T; Ogg, R

2014-06-01

Purpose: To assess early effects of proton therapy on the structural integrity of cerebral white matter in relation to the subsequent near-term development of such effects. Methods: Sixteen children (aged 2–19 years) with craniopharyngioma underwent proton therapy of 54 Cobalt Gray Equivalent (CGE) in a prospective therapeutic trial. Diffusion tensor imaging (DTI) was performed at baseline before proton therapy and every 3 months thereafter. Tract-based spatial statics analysis of DTI data was performed to derive the fractional anisotropy (FA) and radial diffusivity (RD) in 26 volumes of interest (VOIs). The dose distributions were spatially normalized to identify VOIs prone tomore » high doses. The longitudinal percentage changes of the FA and RD in these VOIs at 3 and 12 months from the baseline were calculated, and their relationships were evaluated. Results: The average dose was highest to the cerebral peduncle (CP), corticospinal tract (CST) in the pons, pontine crossing tract (PCT), anterior/posterior limbs of the internal capsule (ALIC/PLIC), and genu of the corpus callosum (GCC). It ranged from 33.3 GCE (GCC) to 49.7 GCE (CP). A mild but statistically significant (P<0.05) decline of FA was observed 3 months after proton therapy in all VOIs except the PLIC and ranged from −1.7% (ALIC) to −2.8% (PCT). A significant increase of RD was found in the CP (3.5%) and ALIC (2.1%). The average longitudinal change from the baseline was reduced at 12 months for most VOIs. However, the standard deviation increased, indicating that the temporal pattern varied individually. The follow-up measurements at 3 and 12 months correlated for the CP, CST, PCT, and GCC (P < 0.04). Conclusion: DTI data suggest early (3 months) effects of proton therapy on microstructures in the white matter. The subsequent follow-up indicated individual variation of the changes, which was partly implied by the early effects.« less

TU-EF-304-09: Quantifying the Biological Effects of Therapeutic Protons by LET Spectrum Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guan, F; Bronk, L; Kerr, M

2015-06-15

Purpose: To correlate in vitro cell kill with linear energy transfer (LET) spectra using Monte Carlo simulations and knowledge obtained from previous high-throughput in vitro proton relative biological effectiveness (RBE) measurements. Methods: The Monte Carlo simulation toolkit Geant4 was used to design the experimental setups and perform the dose, dose-averaged LET, and LET spectra calculations. The clonogenic assay was performed using the H460 lung cancer cell line in standard 6-well plates. Using two different experimental setups, the same dose and dose-averaged LET (12.6 keV/µm) was delivered to the cell layer; however, each respective energy or LET spectrum was different. Wemore » quantified the dose contributions from high-LET (≥10 keV/µm, threshold determined by previous RBE measurements) events in the LET spectra separately for these two setups as 39% and 53%. 8 dose levels with 1 Gy increments were delivered. The photon reference irradiation was performed using 6 MV x-rays from a LINAC. Results: The survival curves showed that both proton irradiations demonstrated an increased RBE compared to the reference photon irradiation. Within the proton-irradiated cells, the setup with 53% dose contribution from high-LET events exhibited the higher biological effectiveness. Conclusion: The experimental results indicate that the dose-averaged LET may not be an appropriate indicator to quantify the biological effects of protons when the LET spectrum is broad enough to contain both low- and high-LET events. Incorporating the LET spectrum distribution into robust intensity-modulated proton therapy optimization planning may provide more accurate biological dose distribution than using the dose-averaged LET. NIH Program Project Grant 2U19CA021239-35.« less

Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirai, Takahisa; Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo; Saito, Soichiro

The poly(ADP-ribose) polymerase (PARP)-1 regulates DNA damage responses and promotes base excision repair. PARP inhibitors have been shown to enhance the cytotoxicity of ionizing radiation in various cancer cells and animal models. We have demonstrated that the PARP inhibitor (PARPi) AZD2281 is also an effective radiosensitizer for carbon-ion radiation; thus, we speculated that the PARPi could be applied to a wide therapeutic range of linear energy transfer (LET) radiation as a radiosensitizer. Institutes for biological experiments using proton beam are limited worldwide. This study was performed as a cooperative research at heavy ion medical accelerator in Chiba (HIMAC) in Nationalmore » Institute of Radiological Sciences. HIMAC can generate various ion beams; this enabled us to compare the radiosensitization effect of the PARPi on cells subjected to proton and carbon-ion beams from the same beam line. After physical optimization of proton beam irradiation, the radiosensitization effect of the PARPi was assessed in the human lung cancer cell line, A549, and the pancreatic cancer cell line, MIA PaCa-2. The effect of the PARPi, AZD2281, on radiosensitization to Bragg peak was more significant than that to entrance region. The PARPi increased the number of phosphorylated H2AX (γ-H2AX) foci and enhanced G2/M arrest after proton beam irradiation. This result supports our hypothesis that a PARPi could be applied to a wide therapeutic range of LET radiation by blocking the DNA repair response. - Highlights: • Effective radiosensitizers for particle radiation therapy have not been reported. • PARP inhibitor treatment radiosensitized after proton beam irradiation. • The sensitization at Bragg peak was greater than that at entrance region. • DSB induction and G2/M arrest is involved in the sensitization mechanism.« less

Initial Report of a Prospective Dosimetric and Clinical Feasibility Trial Demonstrates the Potential of Protons to Increase the Therapeutic Ratio in Breast Cancer Compared With Photons.

PubMed

Bradley, Julie A; Dagan, Roi; Ho, Meng Wei; Rutenberg, Michael; Morris, Christopher G; Li, Zuofeng; Mendenhall, Nancy P

2016-05-01

To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer. From 2012 to 2014, 18 women (stage IIA-IIIB) requiring RNI prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73 years). The cohort included breast-conserving therapy (BCT) and mastectomy patients and right- and left-sided cancers. Treatment targets and organs at risk were delineated on computed tomography scans, and PT and conventional plans were developed. Toxicity was prospectively recorded using Common Terminology Criteria for Adverse Events version 4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. The primary endpoint was a reduction in cardiac V5. Median follow-up was 20 months (range, 2-31 months). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Proton therapy alone was used for 10 patients (9 postmastectomy, 1 after BCT) and combined proton-photon in 8 (6 BCT, 2 postmastectomy with immediate expander reconstruction). Proton therapy improved coverage of level 2 axilla (P=.0005). Adequate coverage of internal mammary nodes was consistently achieved with PT (median D95, 50.3 Gy; range, 46.6-52.1 Gy) but not with conventional radiation therapy (median D95, 48.2 Gy; range, 40.8-55 Gy; P=.0005). Median cardiac V5 was 0.6% with PT and 16.3% with conventional radiation (P<.0001). Median ipsilateral lung V5 and V20 were improved with PT (median V5 35.3% vs 60.5% [P<.0001]; and median V20, 21.6% vs 35.5% [P<.0001]). Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. No grade 4+ toxicities developed. Proton therapy for RNI after mastectomy or BCT significantly improves cardiac dose, especially for left-sided patients, and lung V5 and V20 in all patients without excessive acute toxicity. Proton therapy simultaneously improves target coverage for the internal mammary nodes and level 2 axilla, which may positively impact long-term survival in breast cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Proton Therapy Facility Planning From a Clinical and Operational Model.

PubMed

Das, Indra J; Moskvin, Vadim P; Zhao, Qingya; Cheng, Chee-Wai; Johnstone, Peter A

2015-10-01

This paper provides a model for planning a new proton therapy center based on clinical data, referral pattern, beam utilization and technical considerations. The patient-specific data for the depth of targets from skin in each beam angle were reviewed at our center providing megavoltage photon external beam and proton beam therapy respectively. Further, data on insurance providers, disease sites, treatment depths, snout size and the beam angle utilization from the patients treated at our proton facility were collected and analyzed for their utilization and their impact on the facility cost. The most common disease sites treated at our center are head and neck, brain, sarcoma and pediatric malignancies. From this analysis, it is shown that the tumor depth from skin surface has a bimodal distribution (peak at 12 and 26 cm) that has significant impact on the maximum proton energy, requiring the energy in the range of 130-230 MeV. The choice of beam angles also showed a distinct pattern: mainly at 90° and 270°; this indicates that the number of gantries may be minimized. Snout usage data showed that 70% of the patients are treated with 10 cm snouts. The cost of proton beam therapy depends largely on the type of machine, maximum beam energy and the choice of gantry versus fixed beam line. Our study indicates that for a 4-room center, only two gantry rooms could be needed at the present pattern of the patient cohorts, thus significantly reducing the initial capital cost. In the USA, 95% and 100% of patients can be treated with 200 and 230 MeV proton beam respectively. Use of multi-leaf collimators and pencil beam scanning may further reduce the operational cost of the facility. © The Author(s) 2014.

Poster - 40: Treatment Verification of a 3D-printed Eye Phantom for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunning, Chelsea; Lindsay, Clay; Unick, Nick

Purpose: Ocular melanoma is a form of eye cancer which is often treated using proton therapy. The benefit of the steep proton dose gradient can only be leveraged for accurate patient eye alignment. A treatment-planning program was written to plan on a 3D-printed anatomical eye-phantom, which was then irradiated to demonstrate the feasibility of verifying in vivo dosimetry for proton therapy using PET imaging. Methods: A 3D CAD eye model with critical organs was designed and voxelized into the Monte-Carlo transport code FLUKA. Proton dose and PET isotope production were simulated for a treatment plan of a test tumour, generatedmore » by a 2D treatment-planning program developed using NumPy and proton range tables. Next, a plastic eye-phantom was 3D-printed from the CAD model, irradiated at the TRIUMF Proton Therapy facility, and imaged using a PET scanner. Results: The treatment-planning program prediction of the range setting and modulator wheel was verified in FLUKA to treat the tumour with at least 90% dose coverage for both tissue and plastic. An axial isotope distribution of the PET isotopes was simulated in FLUKA and converted to PET scan counts. Meanwhile, the 3D-printed eye-phantom successfully yielded a PET signal. Conclusions: The 2D treatment-planning program can predict required parameters to sufficiently treat an eye tumour, which was experimentally verified using commercial 3D-printing hardware to manufacture eye-phantoms. Comparison between the simulated and measured PET isotope distribution could provide a more realistic test of eye alignment, and a variation of the method using radiographic film is being developed.« less

Preliminary results of an in-beam PET prototype for proton therapy

NASA Astrophysics Data System (ADS)

Attanasi, F.; Belcari, N.; Camarda, M.; Cirrone, G. A. P.; Cuttone, G.; Del Guerra, A.; Di Rosa, F.; Lanconelli, N.; Rosso, V.; Russo, G.; Vecchio, S.

2008-06-01

Proton therapy can overcome the limitations of conventional radiotherapy due to the more selective energy deposition in depth and to the increased biological effectiveness. Verification of the delivered dose is desirable, but the complete stopping of the protons in patient prevents the application of electronic portal imaging methods that are used in conventional radiotherapy During proton therapy β + emitters like 11C, 15O, 10C are generated in irradiated tissues by nuclear reactions. The measurement of the spatial distribution of this activity, immediately after patient irradiation, can lead to information on the effective delivered dose. First, results of a feasibility study of an in-beam PET for proton therapy are reported. The prototype is based on two planar heads with an active area of about 5×5 cm 2. Each head is made up of a position sensitive photomultiplier coupled to a square matrix of same size of LYSO scintillating crystals (2×2×18 mm 3 pixel dimensions). Four signals from each head are acquired through a dedicated electronic board that performs signal amplification and digitization. A 3D reconstruction of the activity distribution is calculated using an expectation maximization algorithm. To characterize the PET prototype, the detection efficiency and the spatial resolution were measured using a point-like radioactive source. The validation of the prototype was performed using 62 MeV protons at the CATANA beam line of INFN LNS and PMMA phantoms. Using the full energy proton beam and various range shifters, a good correlation between the position of the activity distal edge and the thickness of the beam range shifter was found along the axial direction.

The University of Texas M.D. Anderson Cancer Center Proton Therapy Facility

NASA Astrophysics Data System (ADS)

Smith, Alfred; Newhauser, Wayne; Latinkic, Mitchell; Hay, Amy; McMaken, Bruce; Styles, John; Cox, James

2003-08-01

The University of Texas M.D. Anderson Cancer Center (MDACC), in partnership with Sanders Morris Harris Inc., a Texas-based investment banking firm, and The Styles Company, a developer and manager of hospitals and healthcare facilities, is building a proton therapy facility near the MDACC main complex at the Texas Medical Center in Houston, Texas USA. The MDACC Proton Therapy Center will be a freestanding, investor-owned radiation oncology center offering state-of-the-art proton beam therapy. The facility will have four treatment rooms: three rooms will have rotating, isocentric gantries and the fourth treatment room will have capabilities for both large and small field (e.g. ocular melanoma) treatments using horizontal beam lines. There will be an additional horizontal beam room dedicated to physics research and development, radiation biology research, and outside users who wish to conduct experiments using proton beams. The first two gantries will each be initially equipped with a passive scattering nozzle while the third gantry will have a magnetically swept pencil beam scanning nozzle. The latter will include enhancements to the treatment control system that will allow for the delivery of proton intensity modulation treatments. The proton accelerator will be a 250 MeV zero-gradient synchrotron with a slow extraction system. The facility is expected to open for patient treatments in the autumn of 2005. It is anticipated that 675 patients will be treated during the first full year of operation, while full capacity, reached in the fifth year of operation, will be approximately 3,400 patients per year. Treatments will be given up to 2-shifts per day and 6 days per week.

The potential of intensity-modulated proton radiotherapy to reduce swallowing dysfunction in the treatment of head and neck cancer: A planning comparative study.

PubMed

van der Laan, Hans Paul; van de Water, Tara A; van Herpt, Heleen E; Christianen, Miranda E M C; Bijl, Hendrik P; Korevaar, Erik W; Rasch, Coen R; van 't Veld, Aart A; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A

2013-04-01

Predictive models for swallowing dysfunction were developed previously and showed the potential of improved intensity-modulated radiotherapy to reduce the risk of swallowing dysfunction. Still the risk is high. The aim of this study was to determine the potential of swallowing-sparing (SW) intensity-modulated proton therapy (IMPT) in head and neck cancer (HNC) for reducing the risk of swallowing dysfunction relative to currently used photon therapy. Twenty-five patients with oropharyngeal (n = 21) and hypopharyngeal (n = 4) cancer received primary radiotherapy, including bilateral neck irradiation, using standard (ST) intensity-modulated photon therapy (IMRT). Prophylactic (54 Gy) and therapeutic (70 Gy) target volumes were defined. The dose to the parotid and submandibular glands was reduced as much as possible. Four additional radiotherapy plans were created for each patient: SW-IMRT, ST-IMPT, 3-beam SW-IMPT (3B-SW-IMPT) and 7-beam SW-IMPT (7B-SW-IMPT). All plans were optimized similarly, with additional attempts to spare the swallowing organs at risk (SWOARs) in the SW plans. Probabilities of swallowing dysfunction were calculated with recently developed predictive models. All plans complied with standard HNC radiotherapy objectives. The mean parotid gland doses were similar for the ST and SW photon plans, but clearly lower in all IMPT plans (ipsilateral parotid gland ST-IMRT: 46 Gy, 7B-SW-IMPT: 29 Gy). The mean dose in the SWOARs was lowest with SW-IMPT, in particular with 7B-SW-IMPT (supraglottic larynx ST-IMRT: 60 Gy, 7B-SW-IMPT: 40 Gy). The observed dose reductions to the SWOARs translated into substantial overall reductions in normal tissue complication risks for different swallowing dysfunction endpoints. Compared with ST-IMRT, the risk of physician-rated grade 2-4 swallowing dysfunction was reduced on average by 8.8% (95% CI 6.5-11.1%) with SW-IMRT, and by 17.2% (95% CI: 12.7-21.7%) with 7B-SW-IMPT. SWOAR-sparing with proton therapy has the potential to substantially reduce the risk of swallowing dysfunction compared to similar treatment with photons.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, M; Depauw, N; Kooy, H

Purpose: To investigate the dosimetric benefits of pencil beam scanning (PBS) compared with passive scattered (PS) proton therapy for treatment of pediatric head&neck patients as a function of the PBS spot size and explore the advantages of using apertures in PBS. Methods: Ten pediatric patients with head&neck cancers treated by PS proton therapy at our institution were retrospectively selected. The histologies included rhabdomyosarcoma, ependymoma, astrocytoma, craniopharyngioma and germinoma. The prescribed dose ranged from 36 to 54 Gy(RBE). Five PBS plans were created for each patient using variable spot size (average sigma at isocenter) and choice of beam specific apertures: (1)more » 10mm spots, (2) 10mm spots with apertures, (3) 6mm spots, (4) 6mm spots with apertures, and (5) 3mm spots. The plans were optimized for intensity modulated proton therapy (IMPT) with no single beam uniformity constraints. Dose volume indices as well as equivalent uniform dose (EUD) were compared between PS and PBS plans. Results: Although target coverage was clinically adequate for all cases, the plans with largest (10mm) spots provide inferior quality compared with PS in terms of dose to organs-at-risk (OAR). However, adding apertures to these plans ensured lower OAR dose than PS. The average EUD difference between PBS and PS plans over all patients and organs at risk were (1) 2.5%, (2) −5.1%, (3) -5%, (4) −7.8%, and (5) −9.5%. As the spot size decreased, more conformal plans were achieved that offered similar target coverage but lower dose to the neighboring healthy organs, while alleviating the need for using apertures. Conclusion: The application of PBS does not always translate to better plan qualities compared to PS depending on the available beam spot size. We recommend that institutions with spot size larger than ∼6mm at isocenter consider using apertures to guarantee clinically comparable or superior dosimetric efficacy to PS treatments.« less

SU-F-T-157: Physics Considerations Regarding Dosimetric Accuracy of Analytical Dose Calculations for Small Field Proton Therapy: A Monte Carlo Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, C; Nanjing University of Aeronautics and Astronautics, Nanjing; Daartz, J

Purpose: To evaluate the accuracy of dose calculations by analytical dose calculation methods (ADC) for small field proton therapy in a gantry based passive scattering facility. Methods: 50 patients with intra-cranial disease were evaluated in the study. Treatment plans followed standard prescription and optimization procedures of proton stereotactic radiosurgery. Dose distributions calculated with the Monte Carlo (MC) toolkit TOPAS were used to represent delivered treatments. The MC dose was first adjusted using the output factor (OF) applied clinically. This factor is determined from the field size and the prescribed range. We then introduced a normalization factor to measure the differencemore » in mean dose between the delivered dose (MC dose with OF) and the dose calculated by ADC for each beam. The normalization was determined by the mean dose of the center voxels of the target area. We compared delivered dose distributions and those calculated by ADC in terms of dose volume histogram parameters and beam range distributions. Results: The mean target dose for a whole treatment is generally within 5% comparing delivered dose (MC dose with OF) and ADC dose. However, the differences can be as great as 11% for shallow and small target treated with a thick range compensator. Applying the normalization factor to the MC dose with OF can reduce the mean dose difference to less than 3%. Considering range uncertainties, the generally applied margins (3.5% of the prescribed range + 1mm) to cover uncertainties in range might not be sufficient to guarantee tumor coverage. The range difference for R90 (90% distal dose falloff) is affected by multiple factors, such as the heterogeneity index. Conclusion: This study indicates insufficient accuracy calculating proton doses using ADC. Our results suggest that uncertainties of target doses are reduced using MC techniques, improving the dosimetric accuracy for proton stereotactic radiosurgery. The work was supported by NIH/NCI under CA U19 021239. CG was partially supported by the Chinese Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087).« less

Modern medical and surgical management of difficult-to-treat GORD

PubMed Central

Sifrim, Daniel; Tutuian, Radu; Attwood, Stephen; Lundell, Lars

2013-01-01

Approximately 30–40% of patients taking proton pump inhibitors (PPIs) for presumed gastro-oesophageal reflux (GOR) symptoms do not achieve adequate symptom control, especially when no oesophageal mucosal breaks are present at endoscopy and when extra-oesophageal symptoms are concerned. After failure of optimization of medical therapy, a careful work up is mandatory that aims at determining whether symptoms are related to GOR or not. Most patients with refractory symptoms do not have GOR-related symptoms. Some may have symptoms related to weakly acidic reflux and/or oesophageal hypersensitivity. Baclofen is currently the only antireflux compound available as add-on therapy to PPIs, but its poor tolerability limits its use in clinical practice. There is room for pain modulators in patients with hypersensitive oesophagus and functional heartburn. Antireflux surgery is a suitable option in patients responding to medical therapy who want to avoid taking medication or if persisting symptoms can be clearly attributed to poorly controlled GOR. PMID:24917938

SU-E-T-656: Quantitative Analysis of Proton Boron Fusion Therapy (PBFT) in Various Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, D; Jung, J; Shin, H

2015-06-15

Purpose: Three alpha particles are concomitant of proton boron interaction, which can be used in radiotherapy applications. We performed simulation studies to determine the effectiveness of proton boron fusion therapy (PBFT) under various conditions. Methods: Boron uptake regions (BURs) of various widths and densities were implemented in Monte Carlo n-particle extended (MCNPX) simulation code. The effect of proton beam energy was considered for different BURs. Four simulation scenarios were designed to verify the effectiveness of integrated boost that was observed in the proton boron reaction. In these simulations, the effect of proton beam energy was determined for different physical conditions,more » such as size, location, and boron concentration. Results: Proton dose amplification was confirmed for all proton beam energies considered (< 96.62%). Based on the simulation results for different physical conditions, the threshold for the range in which proton dose amplification occurred was estimated as 0.3 cm. Effective proton boron reaction requires the boron concentration to be equal to or greater than 14.4 mg/g. Conclusion: We established the effects of the PBFT with various conditions by using Monte Carlo simulation. The results of our research can be used for providing a PBFT dose database.« less

A CW FFAG for Proton Computed Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnstone, C.; Neuffer, D. V.; Snopok, P.

2012-05-01

An advantage of the cyclotron in proton therapy is the continuous (CW) beam output which reduces complexity and response time in the dosimetry requirements and beam controls. A CW accelerator requires isochronous particle orbits at all energie s through the acceleration cycle and present compact isochronous cyclotrons for proton therapy reach only 250 MeV (kinetic energy) which is required for patient treatment, but low for full Proton Computed Tomography (PCT) capability. PCT specifications ne ed 300-330 MeV in order for protons to transit the human body. Recent innovations in nonscaling FFAG design have achieved isochronous performance in a compact (~3more » m radius) design at these higher energies. Preliminary isochronous designs are presented her e. Lower energy beams can be efficiently extracted for patient treatment without changes to the acceleration cycle and magnet currents.« less

Compton Camera and Prompt Gamma Ray Timing: Two Methods for In Vivo Range Assessment in Proton Therapy

PubMed Central

Hueso-González, Fernando; Fiedler, Fine; Golnik, Christian; Kormoll, Thomas; Pausch, Guntram; Petzoldt, Johannes; Römer, Katja E.; Enghardt, Wolfgang

2016-01-01

Proton beams are promising means for treating tumors. Such charged particles stop at a defined depth, where the ionization density is maximum. As the dose deposit beyond this distal edge is very low, proton therapy minimizes the damage to normal tissue compared to photon therapy. Nevertheless, inherent range uncertainties cast doubts on the irradiation of tumors close to organs at risk and lead to the application of conservative safety margins. This constrains significantly the potential benefits of protons over photons. In this context, several research groups are developing experimental tools for range verification based on the detection of prompt gammas, a nuclear by-product of the proton irradiation. At OncoRay and Helmholtz-Zentrum Dresden-Rossendorf, detector components have been characterized in realistic radiation environments as a step toward a clinical Compton camera. On the one hand, corresponding experimental methods and results obtained during the ENTERVISION training network are reviewed. On the other hand, a novel method based on timing spectroscopy has been proposed as an alternative to collimated imaging systems. The first tests of the timing method at a clinical proton accelerator are summarized, its applicability in a clinical environment for challenging the current safety margins is assessed, and the factors limiting its precision are discussed. PMID:27148473

Characterization of the proton irradiation induced luminescence of materials and application in radiation oncology dosimetry

NASA Astrophysics Data System (ADS)

Darafsheh, Arash; Zhang, Rongxiao; Kassaee, Alireza; Finlay, Jarod C.

2018-03-01

Visible light generated as the result of interaction of ionizing radiation with matter can be used for radiation therapy quality assurance. In this work, we characterized the visible light observed during proton irradiation of poly(methyl methacrylate) (PMMA) and silica glass fiber materials by performing luminescence spectroscopy. The spectra of the luminescence signal from PMMA and silica glass fibers during proton irradiation showed continuous spectra whose shape were different from that expected from Čerenkov radiation, indicating that Čerenkov radiation cannot be the responsible radioluminescence signal. The luminescence signal from each material showed a Bragg peak pattern and their corresponding proton ranges are in agreement with measurements performed by a standard ion chamber. The spectrum of the silica showed two peaks at 460 and 650 nm stem from the point defects of the silica: oxygen deficiency centers (ODC) and non-bridging oxygen hole centers (NBOHC), respectively. The spectrum of the PMMA fiber showed a continuous spectrum with a peak at 410 nm whose origin is connected with the fluorescence of the PMMA material. Our results are of interest for various applications based on imaging radioluminescent signal in proton therapy and will inform on the design of high-resolution fiber probes for proton therapy dosimetry.

Efficiency of analytical and sampling-based uncertainty propagation in intensity-modulated proton therapy

NASA Astrophysics Data System (ADS)

Wahl, N.; Hennig, P.; Wieser, H. P.; Bangert, M.

2017-07-01

The sensitivity of intensity-modulated proton therapy (IMPT) treatment plans to uncertainties can be quantified and mitigated with robust/min-max and stochastic/probabilistic treatment analysis and optimization techniques. Those methods usually rely on sparse random, importance, or worst-case sampling. Inevitably, this imposes a trade-off between computational speed and accuracy of the uncertainty propagation. Here, we investigate analytical probabilistic modeling (APM) as an alternative for uncertainty propagation and minimization in IMPT that does not rely on scenario sampling. APM propagates probability distributions over range and setup uncertainties via a Gaussian pencil-beam approximation into moments of the probability distributions over the resulting dose in closed form. It supports arbitrary correlation models and allows for efficient incorporation of fractionation effects regarding random and systematic errors. We evaluate the trade-off between run-time and accuracy of APM uncertainty computations on three patient datasets. Results are compared against reference computations facilitating importance and random sampling. Two approximation techniques to accelerate uncertainty propagation and minimization based on probabilistic treatment plan optimization are presented. Runtimes are measured on CPU and GPU platforms, dosimetric accuracy is quantified in comparison to a sampling-based benchmark (5000 random samples). APM accurately propagates range and setup uncertainties into dose uncertainties at competitive run-times (GPU ≤slant {5} min). The resulting standard deviation (expectation value) of dose show average global γ{3% / {3}~mm} pass rates between 94.2% and 99.9% (98.4% and 100.0%). All investigated importance sampling strategies provided less accuracy at higher run-times considering only a single fraction. Considering fractionation, APM uncertainty propagation and treatment plan optimization was proven to be possible at constant time complexity, while run-times of sampling-based computations are linear in the number of fractions. Using sum sampling within APM, uncertainty propagation can only be accelerated at the cost of reduced accuracy in variance calculations. For probabilistic plan optimization, we were able to approximate the necessary pre-computations within seconds, yielding treatment plans of similar quality as gained from exact uncertainty propagation. APM is suited to enhance the trade-off between speed and accuracy in uncertainty propagation and probabilistic treatment plan optimization, especially in the context of fractionation. This brings fully-fledged APM computations within reach of clinical application.

Efficiency of analytical and sampling-based uncertainty propagation in intensity-modulated proton therapy.

PubMed

Wahl, N; Hennig, P; Wieser, H P; Bangert, M

2017-06-26

The sensitivity of intensity-modulated proton therapy (IMPT) treatment plans to uncertainties can be quantified and mitigated with robust/min-max and stochastic/probabilistic treatment analysis and optimization techniques. Those methods usually rely on sparse random, importance, or worst-case sampling. Inevitably, this imposes a trade-off between computational speed and accuracy of the uncertainty propagation. Here, we investigate analytical probabilistic modeling (APM) as an alternative for uncertainty propagation and minimization in IMPT that does not rely on scenario sampling. APM propagates probability distributions over range and setup uncertainties via a Gaussian pencil-beam approximation into moments of the probability distributions over the resulting dose in closed form. It supports arbitrary correlation models and allows for efficient incorporation of fractionation effects regarding random and systematic errors. We evaluate the trade-off between run-time and accuracy of APM uncertainty computations on three patient datasets. Results are compared against reference computations facilitating importance and random sampling. Two approximation techniques to accelerate uncertainty propagation and minimization based on probabilistic treatment plan optimization are presented. Runtimes are measured on CPU and GPU platforms, dosimetric accuracy is quantified in comparison to a sampling-based benchmark (5000 random samples). APM accurately propagates range and setup uncertainties into dose uncertainties at competitive run-times (GPU [Formula: see text] min). The resulting standard deviation (expectation value) of dose show average global [Formula: see text] pass rates between 94.2% and 99.9% (98.4% and 100.0%). All investigated importance sampling strategies provided less accuracy at higher run-times considering only a single fraction. Considering fractionation, APM uncertainty propagation and treatment plan optimization was proven to be possible at constant time complexity, while run-times of sampling-based computations are linear in the number of fractions. Using sum sampling within APM, uncertainty propagation can only be accelerated at the cost of reduced accuracy in variance calculations. For probabilistic plan optimization, we were able to approximate the necessary pre-computations within seconds, yielding treatment plans of similar quality as gained from exact uncertainty propagation. APM is suited to enhance the trade-off between speed and accuracy in uncertainty propagation and probabilistic treatment plan optimization, especially in the context of fractionation. This brings fully-fledged APM computations within reach of clinical application.

Characterization of the exradin W1 plastic scintillation detector for small field applications in proton therapy.

PubMed

Hoehr, C; Lindsay, C; Beaudry, J; Penner, C; Strgar, V; Lee, R; Duzenli, C

2018-05-04

Accurate dosimetry in small field proton therapy is challenging, particularly for applications such as ocular therapy, and suitable detectors for this purpose are sought. The Exradin W1 plastic scintillating fibre detector is known to out-perform most other detectors for determining relative dose factors for small megavoltage photon beams used in radiotherapy but its potential in small proton beams has been relatively unexplored in the literature. The 1 mm diameter cylindrical geometry and near water equivalence of the W1 makes it an attractive alternative to other detectors. This study examines the dosimetric performance of the W1 in a 74 MeV proton therapy beam with particular focus on detector response characteristics relevant to relative dose measurement in small fields suitable for ocular therapy. Quenching of the scintillation signal is characterized and demonstrated not to impede relative dose measurements at a fixed depth. The background cable-only (Čerenkov and radio-fluorescence) signal is 4 orders of magnitude less than the scintillation signal, greatly simplifying relative dose measurements. Comparison with other detectors and Monte Carlo simulations indicate that the W1 is useful for measuring relative dose factors for field sizes down to 5 mm diameter and shallow spread out Bragg peaks down to 6 mm in depth.

Characterization of the exradin W1 plastic scintillation detector for small field applications in proton therapy

NASA Astrophysics Data System (ADS)

Hoehr, C.; Lindsay, C.; Beaudry, J.; Penner, C.; Strgar, V.; Lee, R.; Duzenli, C.

2018-05-01

Accurate dosimetry in small field proton therapy is challenging, particularly for applications such as ocular therapy, and suitable detectors for this purpose are sought. The Exradin W1 plastic scintillating fibre detector is known to out-perform most other detectors for determining relative dose factors for small megavoltage photon beams used in radiotherapy but its potential in small proton beams has been relatively unexplored in the literature. The 1 mm diameter cylindrical geometry and near water equivalence of the W1 makes it an attractive alternative to other detectors. This study examines the dosimetric performance of the W1 in a 74 MeV proton therapy beam with particular focus on detector response characteristics relevant to relative dose measurement in small fields suitable for ocular therapy. Quenching of the scintillation signal is characterized and demonstrated not to impede relative dose measurements at a fixed depth. The background cable-only (Čerenkov and radio-fluorescence) signal is 4 orders of magnitude less than the scintillation signal, greatly simplifying relative dose measurements. Comparison with other detectors and Monte Carlo simulations indicate that the W1 is useful for measuring relative dose factors for field sizes down to 5 mm diameter and shallow spread out Bragg peaks down to 6 mm in depth.

Online advertising and marketing claims by providers of proton beam therapy: are they guideline-based?

PubMed

Corkum, Mark T; Liu, Wei; Palma, David A; Bauman, Glenn S; Dinniwell, Robert E; Warner, Andrew; Mishra, Mark V; Louie, Alexander V

2018-03-15

Cancer patients frequently search the Internet for treatment options, and hospital websites are seen as reliable sources of knowledge. Guidelines support the use of proton radiotherapy in specific disease sites or on clinical trials. This study aims to evaluate direct-to-consumer advertising content and claims made by proton therapy centre (PTC) websites worldwide. Operational PTC websites in English were identified through the Particle Therapy Co-Operative Group website. Data abstraction of website content was performed independently by two investigators. Eight international guidelines were consulted to determine guideline-based indications for proton radiotherapy. Univariate and multivariate logistic regression models were used to determine the characteristics of PTC websites that indicated proton radiotherapy offered greater disease control or cure rates. Forty-eight PTCs with 46 English websites were identified. 60·9% of PTC websites claimed proton therapy provided improved disease control or cure. U.S. websites listed more indications than international websites (15·5 ± 5·4 vs. 10·4 ± 5·8, p = 0·004). The most common disease sites advertised were prostate (87·0%), head and neck (87·0%) and pediatrics (82·6%), all of which were indicated in least one international guideline. Several disease sites advertised were not present in any consensus guidelines, including pancreatobiliary (52·2%), breast (50·0%), and esophageal (43·5%) cancers. Multivariate analysis found increasing number of disease sites and claiming their centre was a local or regional leader in proton radiotherapy was associated with indicating proton radiotherapy offers greater disease control or cure. Information from PTC websites often differs from recommendations found in international consensus guidelines. As online marketing information may have significant influence on patient decision-making, alignment of such information with accepted guidelines and consensus opinion should be adopted by PTC providers.

A scintillator-based approach to monitor secondary neutron production during proton therapy.

PubMed

Clarke, S D; Pryser, E; Wieger, B M; Pozzi, S A; Haelg, R A; Bashkirov, V A; Schulte, R W

2016-11-01

The primary objective of this work is to measure the secondary neutron field produced by an uncollimated proton pencil beam impinging on different tissue-equivalent phantom materials using organic scintillation detectors. Additionally, the Monte Carlo code mcnpx-PoliMi was used to simulate the detector response for comparison to the measured data. Comparison of the measured and simulated data will validate this approach for monitoring secondary neutron dose during proton therapy. Proton beams of 155- and 200-MeV were used to irradiate a variety of phantom materials and secondary particles were detected using organic liquid scintillators. These detectors are sensitive to fast neutrons and gamma rays: pulse shape discrimination was used to classify each detected pulse as either a neutron or a gamma ray. The mcnpx-PoliMi code was used to simulate the secondary neutron field produced during proton irradiation of the same tissue-equivalent phantom materials. An experiment was performed at the Loma Linda University Medical Center proton therapy research beam line and corresponding models were created using the mcnpx-PoliMi code. The authors' analysis showed agreement between the simulations and the measurements. The simulated detector response can be used to validate the simulations of neutron and gamma doses on a particular beam line with or without a phantom. The authors have demonstrated a method of monitoring the neutron component of the secondary radiation field produced by therapeutic protons. The method relies on direct detection of secondary neutrons and gamma rays using organic scintillation detectors. These detectors are sensitive over the full range of biologically relevant neutron energies above 0.5 MeV and allow effective discrimination between neutron and photon dose. Because the detector system is portable, the described system could be used in the future to evaluate secondary neutron and gamma doses on various clinical beam lines for commissioning and prospective data collection in pediatric patients treated with proton therapy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widesott, Lamberto; Lomax, Antony J.; Schwarz, Marco

Purpose: To assess the quality of dose distributions in real clinical cases for different dimensions of scanned proton pencil beams. The distance between spots (i.e., the grid of delivery) is optimized for each dimension of the pencil beam. Methods: The authors vary the {sigma} of the initial Gaussian size of the spot, from {sigma}{sub x} = {sigma}{sub y} = 3 mm to {sigma}{sub x} = {sigma}{sub y} = 8 mm, to evaluate the impact of the proton beam size on the quality of intensity modulated proton therapy (IMPT) plans. The distance between spots, {Delta}x and {Delta}y, is optimized on themore » spot plane, ranging from 4 to 12 mm (i.e., each spot size is coupled with the best spot grid resolution). In our Hyperion treatment planning system (TPS), constrained optimization is applied with respect to the organs at risk (OARs), i.e., the optimization tries to satisfy the dose objectives in the planning target volume (PTV) as long as all planning objectives for the OARs are met. Three-field plans for a nasopharynx case, two-field plans for a prostate case, and two-field plans for a malignant pleural mesothelioma case are considered in our analysis. Results: For the head and neck tumor, the best grids (i.e., distance between spots) are 5, 4, 6, 6, and 8 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. {sigma} {<=} 5 mm is required for tumor volumes with low dose and {sigma}{<=} 4 mm for tumor volumes with high dose. For the prostate patient, the best grid is 4, 4, 5, 5, and 5 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. Beams with {sigma} > 3 mm did not satisfy our first clinical requirement that 95% of the prescribed dose is delivered to more than 95% of prostate and proximal seminal vesicles PTV. Our second clinical requirement, to cover the distal seminal vesicles PTV, is satisfied for beams as wide as {sigma} = 6 mm. For the mesothelioma case, the low dose PTV prescription is well respected for all values of {sigma}, while there is loss of high dose PTV coverage for {sigma} > 5 mm. The best grids have a spacing of 6, 7, 8, 9, and 12 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. Conclusions: The maximum acceptable proton pencil beam {sigma} depends on the volume treated, the protocol of delivery, and optimization of the plan. For the clinical cases, protocol and optimization used in this analysis, acceptable {sigma}s are {<=} 4 mm for the head and neck tumor, {<=} 3 mm for the prostate tumor and {<=} 6 mm for the malignant pleural mesothelioma. One can apply the same procedure used in this analysis when given a ''class'' of patients, a {sigma} and a clinical protocol to determine the optimal grid spacing.« less

The visible signal responsible for proton therapy dosimetry using bare optical fibers is not Čerenkov radiation.

PubMed

Darafsheh, Arash; Taleei, Reza; Kassaee, Alireza; Finlay, Jarod C

2016-11-01

Proton beam dosimetry using bare plastic optical fibers has emerged as a simple approach to proton beam dosimetry. The source of the signal in this method has been attributed to Čerenkov radiation. The aim of this work was a phenomenological study of the nature of the visible light responsible for the signal in bare fiber optic dosimetry of proton therapy beams. Plastic fiber optic probes embedded in solid water phantoms were irradiated with proton beams of energies 100, 180, and 225 MeV produced by a proton therapy cyclotron. Luminescence spectroscopy was performed by a CCD-coupled spectrometer. The spectra were acquired at various depths in phantom to measure the percentage depth dose (PDD) for each beam energy. For comparison, the PDD curves were acquired using a standard multilayer ion chamber device. In order to further analyze the contribution of the Čerenkov radiation in the spectra, Monte Carlo simulation was performed using fluka Monte Carlo code to stochastically simulate radiation transport, ionizing radiation dose deposition, and optical emission of Čerenkov radiation. The measured depth doses using the bare fiber are in agreement with measurements performed by the multilayer ion chamber device, indicating the feasibility of using bare fiber probes for proton beam dosimetry. The spectroscopic study of proton-irradiated fibers showed a continuous spectrum with a shape different from that of Čerenkov radiation. The Monte Carlo simulations confirmed that the amount of the generated Čerenkov light does not follow the radiation absorbed dose in a medium. The source of the optical signal responsible for the proton dose measurement using bare optical fibers is not Čerenkov radiation. It is fluorescence of the plastic material of the fiber.

SU-E-T-481: Dosimetric Effects of Tissue Heterogeneity in Proton Therapy: Monte Carlo Simulation and Experimental Study Using Animal Tissue Phantoms.

PubMed

Liu, Y; Zheng, Y

2012-06-01

Accurate determination of proton dosimetric effect for tissue heterogeneity is critical in proton therapy. Proton beams have finite range and consequently tissue heterogeneity plays a more critical role in proton therapy. The purpose of this study is to investigate the tissue heterogeneity effect in proton dosimetry based on anatomical-based Monte Carlo simulation using animal tissues. Animal tissues including a pig head and beef bulk were used in this study. Both pig head and beef were scanned using a GE CT scanner with 1.25 mm slice thickness. A treatment plan was created, using the CMS XiO treatment planning system (TPS) with a single proton spread-out-Bragg-peak beam (SOBP). Radiochromic films were placed at the distal falloff region. Image guidance was used to align the phantom before proton beams were delivered according to the treatment plan. The same two CT sets were converted to Monte Carlo simulation model. The Monte Carlo simulated dose calculations with/without tissue omposition were compared to TPS calculations and measurements. Based on the preliminary comparison, at the center of SOBP plane, the Monte Carlo simulation dose without tissue composition agreed generally well with TPS calculation. In the distal falloff region, the dose difference was large, and about 2 mm isodose line shift was observed with the consideration of tissue composition. The detailed comparison of dose distributions between Monte Carlo simulation, TPS calculations and measurements is underway. Accurate proton dose calculations are challenging in proton treatment planning for heterogeneous tissues. Tissue heterogeneity and tissue composition may lead to isodose line shifts up to a few millimeters in the distal falloff region. By simulating detailed particle transport and energy deposition, Monte Carlo simulations provide a verification method in proton dose calculation where inhomogeneous tissues are present. © 2012 American Association of Physicists in Medicine.

[Report on proton therapy according to good clinical practice at Hyogo Ion Beam Medical Center].

PubMed

Murakami, Masao; Kagawa, Kazufumi; Hishikawa, Yoshio; Abe, Mitsuyuki

2002-02-01

The Hyogo Ion Beam Medical Center(HIBMC) is a hospital-based charged particle treatment facility. Having two treatment ion beams(proton and carbon) and five treatment rooms, it is a pioneer among particle institutes worldwide. In May 2001, proton therapy was started as a clinical study for patients with localized cancer originating in the head and neck, lung, liver, and prostate. The aim of this study was to investigate the safety, effectiveness, and stability of the treatment units and systems based on the evaluation of acute toxicity, tumor response, and working ratio of the machine, respectively. Six patients, including liver cancer in three, prostate cancer in two, and lung cancer in one, were treated. There was no cessation of therapy owing to machine malfunction. Full courses of proton therapy consisting of 154 portals in all six patients were given exactly as scheduled. None of the patients experienced severe acute reactions of more than grade 3 according to NCI-CTC criteria. Tumor response one month post-treatment was evaluable in five of the six patients, and was CR in 1 (prostate cancer), PR in 2 (lung cancer: 1, liver cancer: 1), and NC in 2(liver cancer: 2). These results indicate that our treatment units and systems are safe and reliable enough for proton irradiation to be used for several malignant tumors localized in the body.

Prompt gamma ray imaging for verification of proton boron fusion therapy: A Monte Carlo study.

PubMed

Shin, Han-Back; Yoon, Do-Kun; Jung, Joo-Young; Kim, Moo-Sub; Suh, Tae Suk

2016-10-01

The purpose of this study was to verify acquisition feasibility of a single photon emission computed tomography image using prompt gamma rays for proton boron fusion therapy (PBFT) and to confirm an enhanced therapeutic effect of PBFT by comparison with conventional proton therapy without use of boron. Monte Carlo simulation was performed to acquire reconstructed image during PBFT. We acquired percentage depth dose (PDD) of the proton beams in a water phantom, energy spectrum of the prompt gamma rays, and tomographic images, including the boron uptake region (BUR; target). The prompt gamma ray image was reconstructed using maximum likelihood expectation maximisation (MLEM) with 64 projection raw data. To verify the reconstructed image, both an image profile and contrast analysis according to the iteration number were conducted. In addition, the physical distance between two BURs in the region of interest of each BUR was measured. The PDD of the proton beam from the water phantom including the BURs shows more efficient than that of conventional proton therapy on tumour region. A 719keV prompt gamma ray peak was clearly observed in the prompt gamma ray energy spectrum. The prompt gamma ray image was reconstructed successfully using 64 projections. Different image profiles including two BURs were acquired from the reconstructed image according to the iteration number. We confirmed successful acquisition of a prompt gamma ray image during PBFT. In addition, the quantitative image analysis results showed relatively good performance for further study. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells.

PubMed

Wang, Li; Wang, Xiaochun; Li, Yuting; Han, Shichao; Zhu, Jinming; Wang, Xiaofang; Molkentine, David P; Blanchard, Pierre; Yang, Yining; Zhang, Ruiping; Sahoo, Narayan; Gillin, Michael; Zhu, Xiaorong Ronald; Zhang, Xiaodong; Myers, Jeffrey N; Frank, Steven J

2017-04-01

Human papillomavirus (HPV)-positive oropharyngeal carcinomas response better to X-ray therapy (XRT) than HPV-negative disease. Whether HPV status influences the sensitivity of head and neck cancer cells to proton therapy or the relative biological effectiveness (RBE) of protons versus XRT is unknown. Clonogenic survival was used to calculate the RBE; immunocytochemical analysis and neutral comet assay were used to evaluate unrepaired DNA double-strand breaks. HPV-positive cells were more sensitive to protons and the unrepaired double-strand breaks were more numerous in HPV-positive cells than in HPV-negative cells (p < .001). Protons killed more cells than did XRT at all fraction sizes (all RBEs > 1.06). Cell line type and radiation fraction size influenced the RBE. HPV-positive cells were more sensitive to protons than HPV-negative cells maybe through the effects of HPV on DNA damage and repair. The RBE for protons depends more on cell type and fraction size than on HPV status. © 2016 Wiley Periodicals, Inc. Head Neck 39: 708-715, 2017. © 2016 Wiley Periodicals, Inc.

Measurement profiles of nano-scale ion beam for optimized radiation energy losses

NASA Astrophysics Data System (ADS)

Woo, T. H.; Cho, H. S.

2011-10-01

The behavior of charged particles is investigated for nano-scale ion beam therapy using a medical accelerator. Computational work is performed for the Bragg-peak simulation, which is focused on human organ material of pancreas and thyroid. The Results show that the trends of the dose have several different kinds of distributions. Before constructing a heavy ion collider, this study can give us the reliability of the therapeutic effect. Realistic treatment using human organs is calculated in a simple and cost effective manner using the computational code, the Stopping and Range of Ions in Matter 2008 (SRIM 2008). Considering the safety of the therapy, it is suggested to give a patient orient planning of the cancer therapy. The energy losses in ionization and phonon are analyzed, which are the behaviors in the molecular level nano-scopic investigation. The different fluctuations are shown at 150 MeV, where the lowest temperature is found in proton and pancreas case. Finally, the protocol for the radiation therapy is constructed by the simulation in which the procedure for a better therapy is selected. An experimental measurement incorporated with the simulations could be programmed by this protocol.

Establishing Cost-Effective Allocation of Proton Therapy for Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mailhot Vega, Raymond B.; Ishaq, Omar; Raldow, Ann

Purpose: Cardiac toxicity due to conventional breast radiation therapy (RT) has been extensively reported, and it affects both the life expectancy and quality of life of affected women. Given the favorable oncologic outcomes in most women irradiated for breast cancer, it is increasingly paramount to minimize treatment side effects and improve survivorship for these patients. Proton RT offers promise in limiting heart dose, but the modality is costly and access is limited. Using cost-effectiveness analysis, we provide a decision-making tool to help determine which breast cancer patients may benefit from proton RT referral. Methods and Materials: A Markov cohort model wasmore » constructed to compare the cost-effectiveness of proton versus photon RT for breast cancer management. The model was analyzed for different strata of women based on age (40 years, 50 years, and 60 years) and the presence or lack of cardiac risk factors (CRFs). Model entrants could have 1 of 3 health states: healthy, alive with coronary heart disease (CHD), or dead. Base-case analysis assumed CHD was managed medically. No difference in tumor control was assumed between arms. Probabilistic sensitivity analysis was performed to test model robustness and the influence of including catheterization as a downstream possibility within the health state of CHD. Results: Proton RT was not cost-effective in women without CRFs or a mean heart dose (MHD) <5 Gy. Base-case analysis noted cost-effectiveness for proton RT in women with ≥1 CRF at an approximate minimum MHD of 6 Gy with a willingness-to-pay threshold of $100,000/quality-adjusted life-year. For women with ≥1 CRF, probabilistic sensitivity analysis noted the preference of proton RT for an MHD ≥5 Gy with a similar willingness-to-pay threshold. Conclusions: Despite the cost of treatment, scenarios do exist whereby proton therapy is cost-effective. Referral for proton therapy may be cost-effective for patients with ≥1 CRF in cases for which photon plans are unable to achieve an MHD <5 Gy.« less

Proton Therapy At Siteman Cancer Center: The State Of The Art

NASA Astrophysics Data System (ADS)

Bloch, Charles

2011-06-01

Barnes-Jewish Hospital is on the verge of offering proton radiation therapy to its patients. Those treatments will be delivered from the first Monarch 250, a state-of-the-art cyclotron produced by Still River Systems, Inc., Littleton, MA. The accelerator is the world's first superconducting synchrocyclotron, with a field-strength of 10 tesla, providing the smallest accelerator for high-energy protons currently available. On May 14, 2010 it was announced that the first production unit had successfully extracted 250 MeV protons. That unit is scheduled for delivery to the Siteman Cancer Center, an NCI-designated Comprehensive Cancer Center at Washington University School of Medicine. At a weight of 20 tons and with a diameter of less than 2 meters the compact cyclotron will be mounted on a gantry, another first for proton therapy systems. The single-energy system includes 3 contoured scatterers and 14 different range modulators to provide 24 distinct beam delivery configurations. This allows proton fields up to 25 cm in diameter, with a maximum range from 5.5 to 32 cm and spread-out-Bragg-peak extent up to 20 cm. Monte Carlo simulations have been run using MCNPX to simulate the clinical beam properties. Those calculations have been used to commission a commercial treatment planning system prior to final clinical measurements. MCNPX was also used to calculate the neutron background generated by protons in the scattering system and patient. Additional details of the facility and current status will be presented.

Determination of the depth dose distribution of proton beam using PRESAGE TM dosimeter

NASA Astrophysics Data System (ADS)

Zhao, L.; Das, I. J.; Zhao, Q.; Thomas, A.; Adamovics, J.; Oldman, M.

2010-11-01

PRESAGETM dosimeter dosimeter has been proved useful for 3D dosimetry in conventional photon therapy and IMRT [1-5]. Our objective is to examine the use of PRESAGETM dosimeter for verification of depth dose distribution in proton beam therapy. Three PRESAGETM samples were irradiated with a 79 MeV un-modulated proton beam. Percent depth dose profile measured from the PRESAGETM dosimeter is compared with data obtained in a water phantom using a parallel plate Advanced Markus chamber. The Bragg-peak position determined from the PRESAGETM is within 2 mm compared to measurements in water. PRESAGETM shows a highly linear response to proton dose. However, PRESAGETM also reveals an underdosage around the Bragg peak position due to LET effects. Depth scaling factor and quenching correction factor need further investigation. Our initial result shows that PRESAGETM has promising dosimetric characteristics that could be suitable for proton beam dosimetry.

ERK/p38 MAPK inhibition reduces radio-resistance to a pulsed proton beam in breast cancer stem cells

NASA Astrophysics Data System (ADS)

Jung, Myung-Hwan; Park, Jeong Chan

2015-10-01

Recent studies have identified highly tumorigenic cells with stem cell-like characteristics, termed cancer stem cells (CSCs) in human cancers. CSCs are resistant to conventional radiotherapy and chemotherapy owing to their high DNA repair ability and oncogene overexpression. However, the mechanisms regulating CSC radio-resistance, particularly proton beam resistance, remain unclear. We isolated CSCs from the breast cancer cell lines MCF-7 and MDA-MB-231, which expressed the characteristic breast CSC membrane protein markers CD44+/CD24-/ low , and irradiated the CSCs with pulsed proton beams. We confirmed that CSCs were resistant to pulsed proton beams and showed that treatment with p38 and ERK inhibitors reduced CSC radio-resistance. Based on these results, BCSC radio-resistance can be reduced during proton beam therapy by co-treatment with ERK1/2 or p38 inhibitors, a novel approach to breast cancer therapy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorissen, BL; Giantsoudi, D; Unkelbach, J

Purpose: Cell survival experiments suggest that the relative biological effectiveness (RBE) of proton beams depends on linear energy transfer (LET), leading to higher RBE near the end of range. With intensity-modulated proton therapy (IMPT), multiple treatment plans that differ in the dose contribution per field may yield a similar physical dose distribution, but the RBE-weighted dose distribution may be disparate. RBE models currently do not have the required predictive power to be included in an optimization model due to the variations in experimental data. We propose an LET-based planning method that guides IMPT optimization models towards plans with reduced RBE-weightedmore » dose in surrounding organs at risk (OARs) compared to inverse planning based on physical dose alone. Methods: Optimization models for physical dose are extended with a term for dose times LET (doseLET). Monte Carlo code is used to generate the physical dose and doseLET distribution of each individual pencil beam. The method is demonstrated for an atypical meningioma patient where the target volume abuts the brainstem and partially overlaps with the optic nerve. Results: A reference plan optimized based on physical dose alone yields high doseLET values in parts of the brainstem and optic nerve. Minimizing doseLET in these critical structures as an additional planning goal reduces the risk of high RBE-weighted dose. The resulting treatment plan avoids the distal fall-off of the Bragg peaks for shaping the dose distribution in front of critical stuctures. The maximum dose in the OARs evaluated with RBE models from literature is reduced by 8–14\\% with our method compared to conventional planning. Conclusion: LET-based inverse planning for IMPT offers the ability to reduce the RBE-weighted dose in OARs without sacrificing target dose. This project was in part supported by NCI - U19 CA 21239.« less

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loew, G.H.; Axe, F.U.; Collins, J.R.

In this study, we have investigated the plausibility of a key postulated transformation of the proximal imidazole ligand (His 175) to an imidazolate by proton transfer to a nearby aspartate (Asp 235) absent in Mb. The proton relay system studied included not only models for the His 175 and Asp 235 residues but also for a nearby Trp 191 residue that could also interact with Asp 235 through hydrogen bonding and polarization. Two semiempirical quantum mechanical methods, Am1 and MNDO/H, with improved capabilities of describing H-bonded systems, were used to calculate the enthalpies of the three tautomeric forms of themore » proton relay system corresponding to the proton on the His, Asp, and Trp, respectively. These calculations were made for several models of the effect of the iron. Relative tautomeric enthalpies were calculated both with H-atom only optimization, keeping the heavy atoms fixed in their X-ray positions, and additional optimization that allowed the model Asp residue to relax. Transition-state enthalpies for the proton transfer from His to Asp were also calculated. The results of these studies suggest that the crucial postulated proton transfer from His to Asp is energetically favored, but only in the presence of the interaction of the iron with the imidazole ligand. Another stable form of the cluster, with competing proton transfer from the Trp to the Asp, was found only when the Asp position was allowed to optimize.« less

A Tandetron as proton injector for the eye tumor therapy in Berlin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roehrich, J.; Damerow, T.; Hahn, W.

2012-02-15

The therapy of eye tumors with fast protons is an excellent tool giving very high local control rates. At the Helmholtz-Zentrum Berlin (HZB) almost 1800 patients were treated since 1998. A 2 MV Tandetron was installed as injector for the k = 132 HZB cyclotron. Using the standard 358 duoplasmatron ion source with direct extraction of negative hydrogen ions an extremely stable proton beam can be delivered, both on the short-term and the long-term scale. The hair-needle filaments made from thoriated tungsten wires have safe operation times of more than 1000 h.

Development of Technology for Image-Guided Proton Therapy

DTIC Science & Technology

2011-10-01

testing proton RBE in the Penn proton beam facility  Assemble equipment and develop data analysis software  Install and test tablet PCs...production  Use dual-energy CT and MRI to determine the composition of materials Year 4 ending 9/30/2011  Measurement of RBE for protons using the...Penn proton beam facility  Measure LET for scattered and scanned beams  Enter forms on tablet PCs Phase 5 Scope of Work Year 1 ending 9

Dosimetric comparison of stopping power calibration with dual-energy CT and single-energy CT in proton therapy treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Jiahua; Penfold, Scott N., E-mail: scott.penfold@adelaide.edu.au

Purpose: The accuracy of proton dose calculation is dependent on the ability to correctly characterize patient tissues with medical imaging. The most common method is to correlate computed tomography (CT) numbers obtained via single-energy CT (SECT) with proton stopping power ratio (SPR). CT numbers, however, cannot discriminate between a change in mass density and change in chemical composition of patient tissues. This limitation can have consequences on SPR calibration accuracy. Dual-energy CT (DECT) is receiving increasing interest as an alternative imaging modality for proton therapy treatment planning due to its ability to discriminate between changes in patient density and chemicalmore » composition. In the current work we use a phantom of known composition to demonstrate the dosimetric advantages of proton therapy treatment planning with DECT over SECT. Methods: A phantom of known composition was scanned with a clinical SECT radiotherapy CT-simulator. The phantom was rescanned at a lower X-ray tube potential to generate a complimentary DECT image set. A set of reference materials similar in composition to the phantom was used to perform a stoichiometric calibration of SECT CT number to proton SPRs. The same set of reference materials was used to perform a DECT stoichiometric calibration based on effective atomic number. The known composition of the phantom was used to assess the accuracy of SPR calibration with SECT and DECT. Intensity modulated proton therapy (IMPT) treatment plans were generated with the SECT and DECT image sets to assess the dosimetric effect of the imaging modality. Isodose difference maps and root mean square (RMS) error calculations were used to assess dose calculation accuracy. Results: SPR calculation accuracy was found to be superior, on average, with DECT relative to SECT. Maximum errors of 12.8% and 2.2% were found for SECT and DECT, respectively. Qualitative examination of dose difference maps clearly showed the dosimetric advantages of DECT imaging, compared to SECT imaging for IMPT dose calculation for the case investigated. Quantitatively, the maximum dose calculation error in the SECT plan was 7.8%, compared to a value of 1.4% in the DECT plan. When considering the high dose target region, the root mean square (RMS) error in dose calculation was 2.1% and 0.4% for SECT and DECT, respectively. Conclusions: DECT-based proton treatment planning in a commercial treatment planning system was successfully demonstrated for the first time. DECT is an attractive imaging modality for proton therapy treatment planning owing to its ability to characterize density and chemical composition of patient tissues. SECT and DECT scans of a phantom of known composition have been used to demonstrate the dosimetric advantages obtainable in proton therapy treatment planning with DECT over the current approach based on SECT.« less

WE-EF-303-10: Single- Detector Proton Radiography as a Portal Imaging Equivalent for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doolan, P; Bentefour, E; Testa, M

2015-06-15

Purpose: In proton therapy, patient alignment is of critical importance due to the sensitivity of the proton range to tissue heterogeneities. Traditionally proton radiography is used for verification of the water-equivalent path length (WEPL), which dictates the depth protons reach. In this work we propose its use for alignment. Additionally, many new proton centers have cone-beam computed tomography in place of beamline X-ray imaging and so proton radiography offers a unique patient alignment verification similar to portal imaging in photon therapy. Method: Proton radiographs of a CIRS head phantom were acquired using the Beam Imaging System (BIS) (IBA, Louvain-la-Neuve) inmore » a horizontal beamline. A scattered beam was produced using a small, dedicated, range modulator (RM) wheel fabricated out of aluminum. The RM wheel was rotated slowly (20 sec/rev) using a stepper motor to compensate for the frame rate of the BIS (120 ms). Dose rate functions (DRFs) over two RM wheel rotations were acquired. Calibration was made with known thicknesses of homogeneous solid water. For each pixel the time width, skewness and kurtosis of the DRFs were computed. The time width was used to compute the object WEPL. In the heterogeneous phantom, the excess skewness and excess kurtosis (i.e. difference from homogeneous cases) were computed and assessed for suitability for patient set up. Results: The technique allowed for the simultaneous production of images that can be used for WEPL verification, showing few internal details, and excess skewness and kurtosis images that can be used for soft tissue alignment. These latter images highlight areas where range mixing has occurred, correlating with phantom heterogeneities. Conclusion: The excess skewness and kurtosis images contain details that are not visible in the WET images. These images, unique to the time-resolved proton radiographic method, could be used for patient set up according to soft tissues.« less

Optimization and evaluation of multiple gating beam delivery in a synchrotron-based proton beam scanning system using a real-time imaging technique.

PubMed

Yamada, Takahiro; Miyamoto, Naoki; Matsuura, Taeko; Takao, Seishin; Fujii, Yusuke; Matsuzaki, Yuka; Koyano, Hidenori; Umezawa, Masumi; Nihongi, Hideaki; Shimizu, Shinichi; Shirato, Hiroki; Umegaki, Kikuo

2016-07-01

To find the optimum parameter of a new beam control function installed in a synchrotron-based proton therapy system. A function enabling multiple gated irradiation in the flat top phase has been installed in a real-time-image gated proton beam therapy (RGPT) system. This function is realized by a waiting timer that monitors the elapsed time from the last gate-off signal in the flat top phase. The gated irradiation efficiency depends on the timer value, Tw. To find the optimum Tw value, gated irradiation efficiency was evaluated for each configurable Tw value. 271 gate signal data sets from 58 patients were used for the simulation. The highest mean efficiency 0.52 was obtained in TW=0.2s. The irradiation efficiency was approximately 21% higher than at TW=0s, which corresponds to ordinary synchrotron operation. The irradiation efficiency was improved in 154 (57%) of the 271 cases. The irradiation efficiency was reduced in 117 cases because the TW value was insufficient or the function introduced an unutilized wait time for the next gate-on signal in the flat top phase. In the actual treatment of a patient with a hepatic tumor at Tw=0.2s, 4.48GyE irradiation was completed within 250s. In contrast, the treatment time of ordinary synchrotron operation was estimated to be 420s. The results suggest that the multiple gated-irradiation function has potential to improve the gated irradiation efficiency and to reduce the treatment time. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A novel dose-based positioning method for CT image-guided proton therapy

PubMed Central

Cheung, Joey P.; Park, Peter C.; Court, Laurence E.; Ronald Zhu, X.; Kudchadker, Rajat J.; Frank, Steven J.; Dong, Lei

2013-01-01

Purpose: Proton dose distributions can potentially be altered by anatomical changes in the beam path despite perfect target alignment using traditional image guidance methods. In this simulation study, the authors explored the use of dosimetric factors instead of only anatomy to set up patients for proton therapy using in-room volumetric computed tomographic (CT) images. Methods: To simulate patient anatomy in a free-breathing treatment condition, weekly time-averaged four-dimensional CT data near the end of treatment for 15 lung cancer patients were used in this study for a dose-based isocenter shift method to correct dosimetric deviations without replanning. The isocenter shift was obtained using the traditional anatomy-based image guidance method as the starting position. Subsequent isocenter shifts were established based on dosimetric criteria using a fast dose approximation method. For each isocenter shift, doses were calculated every 2 mm up to ±8 mm in each direction. The optimal dose alignment was obtained by imposing a target coverage constraint that at least 99% of the target would receive at least 95% of the prescribed dose and by minimizing the mean dose to the ipsilateral lung. Results: The authors found that 7 of 15 plans did not meet the target coverage constraint when using only the anatomy-based alignment. After the authors applied dose-based alignment, all met the target coverage constraint. For all but one case in which the target dose was met using both anatomy-based and dose-based alignment, the latter method was able to improve normal tissue sparing. Conclusions: The authors demonstrated that a dose-based adjustment to the isocenter can improve target coverage and/or reduce dose to nearby normal tissue. PMID:23635262

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres

PubMed Central

Alp, Murat; Cucinotta, Francis A.

2017-01-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (>100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. PMID:28554507

SU-E-T-340: Use of Intensity Modulated Proton Therapy (IMPT) for Reducing the Dose to Cochlea in Craniospinal Irradiation (CSI) of Pediatric Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dormer, J; Kassaee, A; Lin, H

2014-06-01

Purpose: To evaluate use of intensity modulated proton therapy (IMPT) and number of beams for sparing cochlea in treatment of whole brain for pediatric medulloblastoma patients. Methods: In our institution, craniospinal irradiation patients are treated in supine position on our proton gantries using pencil beam scanning with each beam uniformly covering the target volume (SFUD). Each treatment plan consists of two opposed lateral whole brain fields and one or two spinal fields. For sparing the cochlea for the whole brain treatment, we created three different plans using IMPT for five pediatric patients. The first plan consisted of two lateral fields,more » the second two lateral fields and a superior-inferior field, and the third two lateral fields and two superior oblique fields. Optimization was performed with heavy weights applied to the eye, lens and cochlea while maintaining a dose prescription of 36 Gy to the whole brain. Results: IMPT plans reduce the dose to the cochlea. Increasing the number of treatment fields was found to lower the average dose to the cochlea: 15.0, 14.5 and 12.5 Gy for the two-field, three-field, and four-field plans respectively. The D95 for the two-field plan was 98.2%, compared to 100.0% for both the three-field and four-field plan. Coverage in the mid-brain was noticeably better in the three- and four-field plans, with more dose conformality surrounding the cochlea. Conclusion: IMPT plans for CSI and the whole brain irradiations are capable of sparing cochlea and reduce the dose considerably without compromising treating brain tissues. The reduction in average dose increases with three and four field plans as compared to traditional two lateral beam plans.« less

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres

NASA Astrophysics Data System (ADS)

Alp, Murat; Cucinotta, Francis A.

2017-05-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch.

Technical Note: A treatment plan comparison between dynamic collimation and a fixed aperture during spot scanning proton therapy for brain treatment

PubMed Central

Smith, Blake; Gelover, Edgar; Moignier, Alexandra; Wang, Dongxu; Flynn, Ryan T.; Lin, Liyong; Kirk, Maura; Solberg, Tim; Hyer, Daniel E.

2016-01-01

Purpose: To quantitatively assess the advantages of energy-layer specific dynamic collimation system (DCS) versus a per-field fixed aperture for spot scanning proton therapy (SSPT). Methods: Five brain cancer patients previously planned and treated with SSPT were replanned using an in-house treatment planning system capable of modeling collimated and uncollimated proton beamlets. The uncollimated plans, which served as a baseline for comparison, reproduced the target coverage and organ-at-risk sparing of the clinically delivered plans. The collimator opening for the fixed aperture-based plans was determined from the combined cross sections of the target in the beam’s eye view over all energy layers which included an additional margin equivalent to the maximum beamlet displacement for the respective energy of that energy layer. The DCS-based plans were created by selecting appropriate collimator positions for each row of beam spots during a Raster-style scanning pattern which were optimized to maximize the dose contributions to the target and limited the dose delivered to adjacent normal tissue. Results: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring surrounding the target, averaged 13.65% (range: 11.8%–16.9%) and 5.18% (2.9%–7.1%) for the DCS and fixed aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 21.35% (19.4%–22.6%) and 8.38% (4.7%–12.0%) for the DCS and fixed aperture plans, respectively. Conclusions: The ability of the DCS to provide collimation to each energy layer yielded better conformity in comparison to fixed aperture plans. PMID:27487886

Impact of dose engine algorithm in pencil beam scanning proton therapy for breast cancer.

PubMed

Tommasino, Francesco; Fellin, Francesco; Lorentini, Stefano; Farace, Paolo

2018-06-01

Proton therapy for the treatment of breast cancer is acquiring increasing interest, due to the potential reduction of radiation-induced side effects such as cardiac and pulmonary toxicity. While several in silico studies demonstrated the gain in plan quality offered by pencil beam scanning (PBS) compared to passive scattering techniques, the related dosimetric uncertainties have been poorly investigated so far. Five breast cancer patients were planned with Raystation 6 analytical pencil beam (APB) and Monte Carlo (MC) dose calculation algorithms. Plans were optimized with APB and then MC was used to recalculate dose distribution. Movable snout and beam splitting techniques (i.e. using two sub-fields for the same beam entrance, one with and the other without the use of a range shifter) were considered. PTV dose statistics were recorded. The same planning configurations were adopted for the experimental benchmark. Dose distributions were measured with a 2D array of ionization chambers and compared to APB and MC calculated ones by means of a γ analysis (agreement criteria 3%, 3 mm). Our results indicate that, when using proton PBS for breast cancer treatment, the Raystation 6 APB algorithm does not allow obtaining sufficient accuracy, especially with large air gaps. On the contrary, the MC algorithm resulted into much higher accuracy in all beam configurations tested and has to be recommended. Centers where a MC algorithm is not yet available should consider a careful use of APB, possibly combined with a movable snout system or in any case with strategies aimed at minimizing air gaps. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Influence of beam incidence and irradiation parameters on stray neutron doses to healthy organs of pediatric patients treated for an intracranial tumor with passive scattering proton therapy.

PubMed

Bonfrate, A; Farah, J; De Marzi, L; Delacroix, S; Hérault, J; Sayah, R; Lee, C; Bolch, W E; Clairand, I

2016-04-01

In scattering proton therapy, the beam incidence, i.e. the patient's orientation with respect to the beam axis, can significantly influence stray neutron doses although it is almost not documented in the literature. MCNPX calculations were carried out to estimate stray neutron doses to 25 healthy organs of a 10-year-old female phantom treated for an intracranial tumor. Two beam incidences were considered in this article, namely a superior (SUP) field and a right lateral (RLAT) field. For both fields, a parametric study was performed varying proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and air gap size. Using a standard beam line configuration for a craniopharyngioma treatment, neutron absorbed doses per therapeutic dose of 63μGyGy(-1) and 149μGyGy(-1) were found at the heart for the SUP and the RLAT fields, respectively. This dose discrepancy was explained by the different patient's orientations leading to changes in the distance between organs and the final collimator where external neutrons are mainly produced. Moreover, investigations on neutron spectral fluence at the heart showed that the number of neutrons was 2.5times higher for the RLAT field compared against the SUP field. Finally, the influence of some irradiation parameters on neutron doses was found to be different according to the beam incidence. Beam incidence was thus found to induce large variations in stray neutron doses, proving that this parameter could be optimized to enhance the radiation protection of the patient. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres.

PubMed

Alp, Murat; Cucinotta, Francis A

2017-05-01

Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100µm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3 He and 12 C particles at energies corresponding to a distance of 1cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. Copyright © 2017. Published by Elsevier Ltd.

Spot size dependence of laser accelerated protons in thin multi-ion foils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Tung-Chang, E-mail: tcliu@umd.edu; Shao, Xi; Liu, Chuan-Sheng

2014-06-15

We present a numerical study of the effect of the laser spot size of a circularly polarized laser beam on the energy of quasi-monoenergetic protons in laser proton acceleration using a thin carbon-hydrogen foil. The used proton acceleration scheme is a combination of laser radiation pressure and shielded Coulomb repulsion due to the carbon ions. We observe that the spot size plays a crucial role in determining the net charge of the electron-shielded carbon ion foil and consequently the efficiency of proton acceleration. Using a laser pulse with fixed input energy and pulse length impinging on a carbon-hydrogen foil, amore » laser beam with smaller spot sizes can generate higher energy but fewer quasi-monoenergetic protons. We studied the scaling of the proton energy with respect to the laser spot size and obtained an optimal spot size for maximum proton energy flux. Using the optimal spot size, we can generate an 80 MeV quasi-monoenergetic proton beam containing more than 10{sup 8} protons using a laser beam with power 250 TW and energy 10 J and a target of thickness 0.15 wavelength and 49 critical density made of 90% carbon and 10% hydrogen.« less

WE-D-17A-01: A Dynamic Collimation System for Spot Scanned Proton Therapy: Conceptual Overview

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyer, D; Hill, P; Wang, D

2014-06-15

Purpose: In the absence of a collimation system, the lateral penumbra in pencil beam scanning (PBS) proton therapy delivered at low energies is highly dependent on the spot size. This dependence, coupled with the fact that spot sizes increase with decreasing energy, reduces the benefit of the PBS technique for treating shallow tumors such as those found in the head and neck region. In order to overcome this limitation, a dynamic collimation system (DCS) was developed for sharpening the lateral penumbra of low energy proton therapy dose distributions delivered by PBS. Methods: The proposed DCS consists of two pairs ofmore » orthogonal trimmer blades which intercept the edges of the proton beam near the target edge in the beam's eye view. Each trimmer blade is capable of rapid motion in the direction perpendicular to the central beam axis by means of a linear motor, with maximum velocity and acceleration of 2.5 m/s and 19.6 m/s{sup 2}, respectively. Two-dimensional treatment plans were created both with and without the DCS for in-air spot sizes (σ-air) of 3, 5, 7, and 9 mm, representing a wide array of clinically available equipment. Results: In its current configuration, the snout of the DCS has outer dimensions of 22.6 × 22.6 cm{sup 2} and is capable of delivering a minimum treatment field size of 15 × 15 cm{sup 2}. Using off the shelf components, the constructed system would weigh less than 20 kg. The treatment plans created with the DCS yielded a reduction in the mean dose to normal tissue surrounding the target of 26.2–40.6% for spot sizes of 3–9 mm, respectively. Conclusion: The DCS can be integrated with current or future proton therapy equipment and we believe it will serve as a useful tool to further improve the next generation of proton therapy delivery.« less

Nonsteroid anti-inflammatory drug-induced gastroduodenal injury.

PubMed

Lai, Larry H; Chan, Francis K L

2009-11-01

This article reviews selected publications related to nonsteroid anti-inflammatory drug (NSAID)-induced gastroduodenal toxicity in recent years. This article provides a comprehensive review of the latest evidence on the epidemiology of NSAID-induced gastroduodenal injury, recommendations on optimal gastroprotective regimens among patients in need of NSAID, risk stratification approach by considering gastrointestinal and cardiovascular risks, and negative interaction between proton pump inhibitors (PPIs) and clopidogrel. Current evidence indicates that a PPI and a cyclooxygenase (COX)-2-selective NSAID provides the best gastric protection. In light of potential cardiovascular hazard of NSAIDs, physicians should select an NSAID according to individual patients' cardiovascular risk (i.e., naproxen vs. a nonnaproxen NSAID). The choice of gastroprotective therapy depends on the number and nature of gastrointestinal risk factors. PPI co-therapy is recommended in patients with high gastrointestinal risk on aspirin. Whether there is any clinically important interaction between PPIs and clopidogrel remains uncertain.

Optimal treatment of laryngopharyngeal reflux disease

PubMed Central

Martinucci, Irene; Savarino, Edoardo; Nacci, Andrea; Romeo, Salvatore Osvaldo; Bellini, Massimo; Savarino, Vincenzo; Fattori, Bruno; Marchi, Santino

2013-01-01

Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A large number of data suggest the growing prevalence of laryngopharyngeal symptoms in patients with gastroesophageal reflux disease. However, laryngopharyngeal reflux is a multifactorial syndrome and gastroesophageal reflux disease is not the only cause involved in its pathogenesis. Current critical issues in diagnosing laryngopharyngeal reflux are many nonspecific laryngeal symptoms and signs, and poor sensitivity and specificity of all currently available diagnostic tests. Although it is a pragmatic clinical strategy to start with empiric trials of proton pump inhibitors, many patients with suspected laryngopharyngeal reflux have persistent symptoms despite maximal acid suppression therapy. Overall, there are scant conflicting results to assess the effect of reflux treatments (including dietary and lifestyle modification, medical treatment, antireflux surgery) on laryngopharyngeal reflux. The present review is aimed at critically discussing the current treatment options in patients with laryngopharyngeal reflux, and provides a perspective on the development of new therapies. PMID:24179671

Assessment of potential advantages of relevant ions for particle therapy: A model based study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grün, Rebecca, E-mail: r.gruen@gsi.de; Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390; Medical Faculty of Philipps-University Marburg, Marburg 35032

2015-02-15

Purpose: Different ion types offer different physical and biological advantages for therapeutic applications. The purpose of this work is to assess the advantages of the most commonly used ions in particle therapy, i.e., carbon ({sup 12}C), helium ({sup 4}He), and protons ({sup 1}H) for different treatment scenarios. Methods: A treatment planning analysis based on idealized target geometries was performed using the treatment planning software TRiP98. For the prediction of the relative biological effectiveness (RBE) that is required for biological optimization in treatment planning the local effect model (LEM IV) was used. To compare the three ion types, the peak-to-entrance ratiomore » (PER) was determined for the physical dose (PER{sub PHY} {sub S}), the RBE (PER{sub RBE}), and the RBE-weighted dose (PER{sub BIO}) resulting for different dose-levels, field configurations, and tissue types. Further, the dose contribution to artificial organs at risk (OAR) was assessed and a comparison of the dose distribution for the different ion types was performed for a patient with chordoma of the skull base. Results: The study showed that the advantages of the ions depend on the physical and biological properties and the interplay of both. In the case of protons, the consideration of a variable RBE instead of the clinically applied generic RBE of 1.1 indicates an advantage in terms of an increased PER{sub RBE} for the analyzed configurations. Due to the fact that protons show a somewhat better PER{sub PHY} {sub S} compared to helium and carbon ions whereas helium shows a higher PER{sub RBE} compared to protons, both protons and helium ions show a similar RBE-weighted dose distribution. Carbon ions show the largest variation of the PER{sub RBE} with tissue type and a benefit for radioresistant tumor types due to their higher LET. Furthermore, in the case of a two-field irradiation, an additional gain in terms of PER{sub BIO} is observed when using an orthogonal field configuration for carbon ions as compared to opposing fields. In contrast, for protons, the PER{sub BIO} is almost independent on the field configuration. Concerning the artificial lateral OAR, the volume receiving 20% of the prescribed RBE-weighted dose (V20) was reduced by over 35% using helium ions and by over 40% using carbon ions compared to protons. The analysis of the patient plan showed that protons, helium, and carbon ions are similar in terms of target coverage whereas the dose to the surrounding tissue is increasing from carbon ions toward protons. The mean dose to the brain stem can be reduced by more than 55% when using helium ions and by further 25% when using carbon ions instead of protons. Conclusions: The comparison of the PER{sub RBE} and PER{sub PHY} {sub S} of the three ion types suggests a strong dependence of the advantages of the three ions on the dose-level, tissue type, and field configuration. In terms of conformity, i.e., dose to the normal tissue, a clear gain is expected using carbon or helium ions compared to protons.« less

Proton Therapy Dose Characterization and Verification

DTIC Science & Technology

2016-10-01

than recommended as these patients are on a separate UPENN research study where dose maximum accepted was 6700 cGy. 15... Research Protection Office. 8.0 Data Handling and Record Keeping All patients must have a signed Informed Consent Form and an On - study (confirmation...this award. Phase 1 concentrated on designing and building a Multi-leaf collimator for use in proton therapy. Phase 2 focused on studying the

Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuaron, John J.; Chon, Brian; Tsai, Henry

Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered wasmore » 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary toxicities.« less

Protective effect of transparent film dressing on proton therapy induced skin reactions.

PubMed

Whaley, Jonathan T; Kirk, Maura; Cengel, Keith; McDonough, James; Bekelman, Justin; Christodouleas, John P

2013-01-24

Proton therapy can result in clinically significant radiation dermatitis. In some clinical scenarios, such as lung or breast cancer, the risk of severe radiation dermatitis may limit beam arrangement and prescription doses. Patients undergoing proton therapy for prostate cancer commonly develop mild radiation dermatitis. Herein, we report the outcomes of two prostate cancer patients whose radiation dermatitis appears to have been substantially diminished by transparent film dressings (Beekley stickers). This is a descriptive report of the skin toxicity observed in two patients undergoing proton therapy for prostate cancer at a single institution in 2011. A phantom dosimetric study was performed to evaluate the impact of a transparent film dressing on a beam's spread out Bragg peak (SOBP). Two patients with low risk prostate cancer were treated with proton therapy to a total dose of 79.2Gy (RBE) in 1.8 Gy (RBE) fractions using two opposed lateral beams daily. Both patients had small circular (2.5 cm diameter) transparent adhesive markers placed on their skin to assist with daily alignment. Patient 1 had markers in place bilaterally for the entirety of treatment. Patient 2 had a marker in place for three weeks on one side and six weeks on the other. Over the course of therapy, both men developed typical Grade 1 radiation dermatitis (asymptomatic erythema) on their hips; however, in both patients, the erythema was substantially decreased beneath the markers. Patient 2 demonstrated less attenuation and thus greater erythema in the skin covered for three weeks compared to the skin covered for six weeks. The difference in skin changes between the covered and uncovered skin persisted for at least 1 month. A phantom study of double scattered beam SOBP with and without the marker in the beam path showed no gross dosimetric effect. Transparent adhesive markers appear to have attenuated radiation dermatitis in these two patients without affecting the SOBP. One patient may have exhibited a dose-response effect. The reproducibility and underlying mechanisms are unclear. However, the potential to leverage this effect to improve proton-related radiation dermatitis in other clinical scenarios is intriguing. Exploratory animal studies are underway.

SU-E-T-280: Dose Evaluation in Using CT Density Versus Relative Stopping Power for Pencil Beam Planning and Treating IROC Proton Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syh, J; Ding, X; Rosen, L

2015-06-15

Purpose: The purpose of this study is to evaluate any effects of converted CT density variation in treatment planning system (TPS) of spot scanning proton therapy with an IROC proton prostate phantom at our new ProteusOne Proton Therapy Center. Methods: A proton prostate phantom was requested from the Imaging and Radiation Oncology Core Houston (IROC), The University of Texas MD Anderson Cancer Center, Houston, TX, where GAF Chromic films and couples of thermo luminescent dosemeter (TLD) capsules in target and adjacent structures were embedded for imaging and dose monitoring. Various material such as PVC, PBT HI polystyrene as dosimetry insertsmore » and acrylic were within phantom. Relative stopping power (SP) were provided. However our treatment planning system (TPS) doesn’t require SP instead relative density was converted relative to water in TPS. Phantom was irradiated and the results were compared with IROC measurements. The range of relative density was converted from SP into relative density of water as a new assigned material and tested. Results: The summary of TLD measurements of the prostate and femoral heads were well within 2% of the TPS and met the criteria established by IROC. The film at coronal plane was found to be shift in superior-inferior direction due to locking position of cylinder insert was off and was corrected. The converted CT density worked precisely to correlated relative stopping power. Conclusion: The proton prostate phantom provided by IROC is a useful methodology to evaluate our new commissioned proton pencil beam and TPS within certain confidence in proton therapy. The relative stopping power was converted into relative physical density relatively to water and the results were satisfied.« less

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation.

PubMed

Girst, S; Marx, C; Bräuer-Krisch, E; Bravin, A; Bartzsch, S; Oelfke, U; Greubel, C; Reindl, J; Siebenwirth, C; Zlobinskaya, O; Multhoff, G; Dollinger, G; Schmid, T E; Wilkens, J J

2015-09-01

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

FoCa: a modular treatment planning system for proton radiotherapy with research and educational purposes

NASA Astrophysics Data System (ADS)

Sánchez-Parcerisa, D.; Kondrla, M.; Shaindlin, A.; Carabe, A.

2014-12-01

FoCa is an in-house modular treatment planning system, developed entirely in MATLAB, which includes forward dose calculation of proton radiotherapy plans in both active and passive modalities as well as a generic optimization suite for inverse treatment planning. The software has a dual education and research purpose. From the educational point of view, it can be an invaluable teaching tool for educating medical physicists, showing the insights of a treatment planning system from a well-known and widely accessible software platform. From the research point of view, its current and potential uses range from the fast calculation of any physical, radiobiological or clinical quantity in a patient CT geometry, to the development of new treatment modalities not yet available in commercial treatment planning systems. The physical models in FoCa were compared with the commissioning data from our institution and show an excellent agreement in depth dose distributions and longitudinal and transversal fluence profiles for both passive scattering and active scanning modalities. 3D dose distributions in phantom and patient geometries were compared with a commercial treatment planning system, yielding a gamma-index pass rate of above 94% (using FoCa’s most accurate algorithm) for all cases considered. Finally, the inverse treatment planning suite was used to produce the first prototype of intensity-modulated, passive-scattered proton therapy, using 13 passive scattering proton fields and multi-leaf modulation to produce a concave dose distribution on a cylindrical solid water phantom without any field-specific compensator.

Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

Herrera, María S.; González, Sara J.; Minsky, Daniel M.; Kreiner, Andrés J.

2010-08-01

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a real patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.

Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrera, Maria S.; Gonzalez, Sara J.; Minsky, Daniel M.

2010-08-04

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a realmore » patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.« less

NTCP modeling analysis of acute hematologic toxicity in whole pelvic radiation therapy for gynecologic malignancies - A dosimetric comparison of IMRT and spot-scanning proton therapy (SSPT).

PubMed

Yoshimura, Takaaki; Kinoshita, Rumiko; Onodera, Shunsuke; Toramatsu, Chie; Suzuki, Ryusuke; Ito, Yoichi M; Takao, Seishin; Matsuura, Taeko; Matsuzaki, Yuka; Umegaki, Kikuo; Shirato, Hiroki; Shimizu, Shinichi

2016-09-01

This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade ⩾3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT). The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45Gy(RBE) in 1.8Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared. The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP=0.04±0.01 and 0.19±0.03, p=0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI=0.97±0.01 and 0.96±0.02, p=0.3177, and HI=1.24±0.11 and 1.27±0.05, p=0.8473, respectively). The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study

PubMed Central

Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

2012-01-01

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2. Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising. PMID:22382688

Spot scanning proton therapy plan assessment: design and development of a dose verification application for use in routine clinical practice

NASA Astrophysics Data System (ADS)

Augustine, Kurt E.; Walsh, Timothy J.; Beltran, Chris J.; Stoker, Joshua B.; Mundy, Daniel W.; Parry, Mark D.; Bues, Martin; Fatyga, Mirek

2016-04-01

The use of radiation therapy for the treatment of cancer has been carried out clinically since the late 1800's. Early on however, it was discovered that a radiation dose sufficient to destroy cancer cells can also cause severe injury to surrounding healthy tissue. Radiation oncologists continually strive to find the perfect balance between a dose high enough to destroy the cancer and one that avoids damage to healthy organs. Spot scanning or "pencil beam" proton radiotherapy offers another option to improve on this. Unlike traditional photon therapy, proton beams stop in the target tissue, thus better sparing all organs beyond the targeted tumor. In addition, the beams are far narrower and thus can be more precisely "painted" onto the tumor, avoiding exposure to surrounding healthy tissue. To safely treat patients with proton beam radiotherapy, dose verification should be carried out for each plan prior to treatment. Proton dose verification systems are not currently commercially available so the Department of Radiation Oncology at the Mayo Clinic developed its own, called DOSeCHECK, which offers two distinct dose simulation methods: GPU-based Monte Carlo and CPU-based analytical. The three major components of the system include the web-based user interface, the Linux-based dose verification simulation engines, and the supporting services and components. The architecture integrates multiple applications, libraries, platforms, programming languages, and communication protocols and was successfully deployed in time for Mayo Clinic's first proton beam therapy patient. Having a simple, efficient application for dose verification greatly reduces staff workload and provides additional quality assurance, ultimately improving patient safety.

Proton Minibeam Radiation Therapy Reduces Side Effects in an In Vivo Mouse Ear Model.

PubMed

Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Zlobinskaya, Olga; Walsh, Dietrich W M; Ilicic, Katarina; Aichler, Michaela; Walch, Axel; Wilkens, Jan J; Multhoff, Gabriele; Dollinger, Günther; Schmid, Thomas E

2016-05-01

Proton minibeam radiation therapy is a novel approach to minimize normal tissue damage in the entrance channel by spatial fractionation while keeping tumor control through a homogeneous tumor dose using beam widening with an increasing track length. In the present study, the dose distributions for homogeneous broad beam and minibeam irradiation sessions were simulated. Also, in an animal study, acute normal tissue side effects of proton minibeam irradiation were compared with homogeneous irradiation in a tumor-free mouse ear model to account for the complex effects on the immune system and vasculature in an in vivo normal tissue model. At the ion microprobe SNAKE, 20-MeV protons were administered to the central part (7.2 × 7.2 mm(2)) of the ear of BALB/c mice, using either a homogeneous field with a dose of 60 Gy or 16 minibeams with a nominal 6000 Gy (4 × 4 minibeams, size 0.18 × 0.18 mm(2), with a distance of 1.8 mm). The same average dose was used over the irradiated area. No ear swelling or other skin reactions were observed at any point after minibeam irradiation. In contrast, significant ear swelling (up to fourfold), erythema, and desquamation developed in homogeneously irradiated ears 3 to 4 weeks after irradiation. Hair loss and the disappearance of sebaceous glands were only detected in the homogeneously irradiated fields. These results show that proton minibeam radiation therapy results in reduced adverse effects compared with conventional homogeneous broad-beam irradiation and, therefore, might have the potential to decrease the incidence of side effects resulting from clinical proton and/or heavy ion therapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

SU-G-TeP3-09: Proton Minibeam Radiation Therapy Increases Normal Tissue Resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prezado, Y; Gonzalez-Infantes, W; Juchaux, M

Purpose: The dose tolerances of normal tissues continue being the main limitation in radiotherapy. To overcome it, we recently proposed a novel concept: proton minibeam radiation therapy (pMBRT) [1]. It allies the physical advantages of protons with the normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams (minibeam radiation therapy) [2]. The dose distributions are such that the tumor receives a homogeneous dose distribution, while normal tissues benefit from the spatial fractionation of the dose. The objective of our work was to implement this promising technique at a clinical center (Proton therapy center in Orsay) in order tomore » evaluate the potential gain in tissue sparing. Methods: Dose distributions were measured by means of gafchromic films and a PTW microdiamond detector (60019). Once the dosimetry was established, the whole brain of 7 weeks old male Fischer 344 rats was irradiated. Half of the animals received conventional seamless proton irradiation (25 Gy in one fraction). The other rats were irradiated with pMBRT (58 Gy peak dose in one fraction). The average dose deposited in the same targeted volume was in both cases 25 Gy. Results: The first complete set of dosimetric data in such small proton field sizes was obtained [3]. Rats treated with conventional proton irradiation exhibited severe moist desquamation and permanent epilation afterwards. The minibeam group, on the other hand, exhibited no skin damage and no clinical symptoms. MRI imaging and histological analysis are planned at 6 months after irradiation. Conclusion: Our preliminary results indicate that pMBRT leads to an increase in tissue resistance. This can open the door to an efficient treatment of very radioresistant tumours. [1] Prezado et al. Med. Phys. 40, 031712, 1–8 (2013).[2] Prezado et al., Rad. Research. 184, 314-21 (2015). [3] Peucelle et al., Med. Phys. 42 7108-13 (2015).« less

Proton or photon irradiation for hemangiomas of the choroid? A retrospective comparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoecht, Stefan; Wachtlin, Joachim; Bechrakis, Nikolaos E.

2006-10-01

Purpose: The aim of this study was to compare, on a retrospective basis, the results of therapy in patients with uveal hemangioma treated with photon or proton irradiation at a single center. Methods and Materials: From 1993 to 2002 a total of 44 patients were treated. Until 1998 radiotherapy was given with 6 MV photons in standard fractionation of 2.0 Gy 5 times per week. In 1998 proton therapy became available and was used since then. A dose of 20 to 22.5 Cobalt Gray Equivalent (CGE) 68 MeV protons was given on 4 consecutive days. Progressive symptoms or deterioration ofmore » vision were the indications for therapy. Results: Of the 44 patients treated, 36 had circumscribed choroidal hemangiomas and 8 had diffuse choroidal hemangiomas (DCH) and Sturge-Weber syndrome. Of the patients, 19 were treated with photons with a total dose in the range of 16 to 30 Gy. A total of 25 patients were irradiated with protons. All patients with DCH but 1 were treated with photons. Stabilization of visual acuity was achieved in 93.2% of all patients. Tumor thickness decreased in 95.4% and retinal detachment resolved in 92.9%. Late effects, although generally mild or moderate, were frequently detected. In all, 40.9% showed radiation-induced optic neuropathy, maximum Grade I. Retinopathy was found in 29.5% of cases, but only 1 patient experienced more than Grade II severity. Retinopathy and radiation-induced optic neuropathy were reversible in some of the patients and in some resolved completely. No differences could be detected between patients with circumscribed choroidal hemangiomas treated with protons and photons. Treatment was less effective in DCH patients (75%). Conclusions: Radiotherapy is effective in treating choroidal hemangiomas with respect to visual acuity and tumor thickness but a benefit of proton therapy could not be detected. Side effects are moderate but careful monitoring for side effects should be part of the follow-up procedures.« less

Quantitative assessment of anatomical change using a virtual proton depth radiograph for adaptive head and neck proton therapy.

PubMed

Wang, Peng; Yin, Lingshu; Zhang, Yawei; Kirk, Maura; Song, Gang; Ahn, Peter H; Lin, Alexander; Gee, James; Dolney, Derek; Solberg, Timothy D; Maughan, Richard; McDonough, James; Teo, Boon-Keng Kevin

2016-03-08

The aim of this work is to demonstrate the feasibility of using water-equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone-beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray-tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beam's eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy.

SU-E-T-470: Importance of HU-Mass Density Calibration Technique in Proton Pencil Beam Dose Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penfold, S; Miller, A

2015-06-15

Purpose: Stoichiometric calibration of Hounsfield Units (HUs) for conversion to proton relative stopping powers (RStPs) is vital for accurate dose calculation in proton therapy. However proton dose distributions are not only dependent on RStP, but also on relative scattering power (RScP) of patient tissues. RScP is approximated from material density but a stoichiometric calibration of HU-density tables is commonly neglected. The purpose of this work was to quantify the difference in calculated dose of a commercial TPS when using HU-density tables based on tissue substitute materials and stoichiometric calibrated ICRU tissues. Methods: Two HU-density calibration tables were generated based onmore » scans of the CIRS electron density phantom. The first table was based directly on measured HU and manufacturer quoted density of tissue substitute materials. The second was based on the same CT scan of the CIRS phantom followed by a stoichiometric calibration of ICRU44 tissue materials. The research version of Pinnacle{sup 3} proton therapy was used to compute dose in a patient CT data set utilizing both HU-density tables. Results: The two HU-density tables showed significant differences for bone tissues; the difference increasing with increasing HU. Differences in density calibration table translated to a difference in calculated RScP of −2.5% for ICRU skeletal muscle and 9.2% for ICRU femur. Dose-volume histogram analysis of a parallel opposed proton therapy prostate plan showed that the difference in calculated dose was negligible when using the two different HU-density calibration tables. Conclusion: The impact of HU-density calibration technique on proton therapy dose calculation was assessed. While differences were found in the calculated RScP of bony tissues, the difference in dose distribution for realistic treatment scenarios was found to be insignificant.« less

Brainstem Cavernous Angioma

MedlinePlus

... echo” (as opposed to spin-echo or proton beam) imaging. Gradient-echo MRI is most efficient at ... radiosurgery for cavernous malformations: Kjellberg's experience with proton beam therapy in 98 cases at the Harvard Cyclotron. ...

The optimal balance between quality and efficiency in proton radiography imaging technique at various proton beam energies: A Monte Carlo study.

PubMed

Biegun, A K; van Goethem, M-J; van der Graaf, E R; van Beuzekom, M; Koffeman, E N; Nakaji, T; Takatsu, J; Visser, J; Brandenburg, S

2017-09-01

Proton radiography is a novel imaging modality that allows direct measurement of the proton energy loss in various tissues. Currently, due to the conversion of so-called Hounsfield units from X-ray Computed Tomography (CT) into relative proton stopping powers (RPSP), the uncertainties of RPSP are 3-5% or higher, which need to be minimized down to 1% to make the proton treatment plans more accurate. In this work, we simulated a proton radiography system, with position-sensitive detectors (PSDs) and a residual energy detector (RED). The simulations were built using Geant4, a Monte Carlo simulation toolkit. A phantom, consisting of several materials was placed between the PSDs of various Water Equivalent Thicknesses (WET), corresponding to an ideal detector, a gaseous detector, silicon and plastic scintillator detectors. The energy loss radiograph and the scattering angle distributions of the protons were studied for proton beam energies of 150MeV, 190MeV and 230MeV. To improve the image quality deteriorated by the multiple Coulomb scattering (MCS), protons with small angles were selected. Two ways of calculating a scattering angle were considered using the proton's direction and position. A scattering angle cut of 8.7mrad was applied giving an optimal balance between quality and efficiency of the radiographic image. For the three proton beam energies, the number of protons used in image reconstruction with the direction method was half the number of protons kept using the position method. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Multicomponent Density Functional Theory: Impact of Nuclear Quantum Effects on Proton Affinities and Geometries.

PubMed

Brorsen, Kurt R; Yang, Yang; Hammes-Schiffer, Sharon

2017-08-03

Nuclear quantum effects such as zero point energy play a critical role in computational chemistry and often are included as energetic corrections following geometry optimizations. The nuclear-electronic orbital (NEO) multicomponent density functional theory (DFT) method treats select nuclei, typically protons, quantum mechanically on the same level as the electrons. Electron-proton correlation is highly significant, and inadequate treatments lead to highly overlocalized nuclear densities. A recently developed electron-proton correlation functional, epc17, has been shown to provide accurate nuclear densities for molecular systems. Herein, the NEO-DFT/epc17 method is used to compute the proton affinities for a set of molecules and to examine the role of nuclear quantum effects on the equilibrium geometry of FHF - . The agreement of the computed results with experimental and benchmark values demonstrates the promise of this approach for including nuclear quantum effects in calculations of proton affinities, pK a 's, optimized geometries, and reaction paths.

Improving proton therapy by metal-containing nanoparticles: nanoscale insights

PubMed Central

Schlathölter, Thomas; Eustache, Pierre; Porcel, Erika; Salado, Daniela; Stefancikova, Lenka; Tillement, Olivier; Lux, Francois; Mowat, Pierre; Biegun, Aleksandra K; van Goethem, Marc-Jan; Remita, Hynd; Lacombe, Sandrine

2016-01-01

The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/μm) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (>2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting. PMID:27143877

Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell–Mediated Killing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gameiro, Sofia R.; Malamas, Anthony S.; Bernstein, Michael B.

Purpose: To provide the foundation for combining immunotherapy to induce tumor antigen–specific T cells with proton radiation therapy to exploit the activity of those T cells. Methods and Materials: Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences. Results: These studies show for the first time that (1) proton and photon radiation induced comparable up-regulation of surface molecules involved in immune recognition (histocompatibilitymore » leukocyte antigen, intercellular adhesion molecule 1, and the tumor-associated antigens carcinoembryonic antigen and mucin 1); (2) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells; and (3) cancer stem cells, which are resistant to the direct cytolytic activity of proton radiation, nonetheless up-regulated calreticulin after radiation in a manner similar to non-cancer stem cells. Conclusions: These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options.« less

Proton beam radiotherapy of uveal melanoma

PubMed Central

Damato, Bertil; Kacperek, Andrzej; Errington, Doug; Heimann, Heinrich

2013-01-01

Proton beam radiotherapy of uveal melanoma can be administered as primary treatment, as salvage therapy for recurrent tumor, and as neoadjuvant therapy prior to surgical resection. The physical properties of proton beams make it possible to deliver high-doses of radiation to the tumor with relative sparing of adjacent tissues. This form of therapy is effective for a wider range of uveal melanoma than any other modality, providing exceptionally-high rates of local tumor control. This is particularly the case with diffuse iris melanomas, many of which are unresectable. The chances of survival, ocular conservation, visual preservation and avoidance of iatrogenic morbidity depend greatly on the tumor size, location and extent. When treating any side-effects and/or complications, it is helpful to consider whether these are the result of collateral damage or persistence of the irradiated tumor (‘toxic tumor syndrome’). PMID:24227980

Transmission calculation and intensity suppression for a proton therapy system

NASA Astrophysics Data System (ADS)

Chen, Wei; Yang, Jun; Qin, Bin; Liang, ZhiKai; Chen, Qushan; Liu, Kaifeng; Li, Dong; Fan, Mingwu

2018-02-01

A proton therapy project HUST-PTF (HUST Proton Therapy Facility) based on a 250 MeV isochronous superconducting cyclotron is under development in Huazhong University of Science and Technology (HUST). In this paper we report the main design features of the beam line in HUST-PTF project. The energy selection system (ESS) for energy modulation is discussed in detail, including the collimators, momentum slit and transmission calculation. Due to significant difference among the transmissions of ESS for different energies, the intensity suppression scheme by defocusing beam at high energies on collimators in the beam line is proposed and discussed. Finally, the ratios of beam intensities between low and high energies are expected to be controlled within 10 to meet the clinical requirement, and the beam optics of each energy step after intensity suppression is studied respectively.

Proton Therapy for Cancer

Cancer.gov

Public interest in this form of radiation therapy is growing, but members of the medical and research communities are concerned that enthusiasm for this promising therapy may be getting ahead of the research.

SU-C-204-02: Behavioral and Pathologic Differences in Mice Exposed to Proton Minibeam Arrays Versus Proton Broad Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eley, J; Zhang, C; Wolfe, T

Purpose: Minibeam therapy using protons or light-ions offers a theoretical reduction of biologic damage to tissues upstream of a tumor compared to broad-beam therapy while providing equal tumor control. The purpose of this study was to investigate behavioral and pathologic differences in mice after exposure of healthy brain to proton minibeam arrays versus proton broad beams. Methods: Twenty-four C57BL/6J juvenile mice were divided into 5 study arms: sham irradiation (NoRT), broad-beam 10 Gy (BB10), minibeam 10Gy (MB10), broad-beam 30 Gy (BB30), and minibeam 30 Gy (MB30), approximate integral entrance doses. Circular beams of 100 MeV protons with 7-mm diameter weremore » delivered laterally through the brain, either as broad beams or as planar minibeam arrays having 300-micron beam width and 1-mm spacing on center. Mice were followed for 8 months using standard behavioral tests. Pathologic studies were carried out at 8 months after irradiation. Results: Peak entrance doses were 10.0, 23.8, 30.0, and 71.3 Gy for mice in BB10, MB10, BB30, and MB30, respectively. Despite the high single-fraction doses, no animals showed signs of radiation sickness or neurophysical impairment over the 8-month study duration. The Morris water maze alternate-starting-position trial showed significant evidence of better spatial learning for mice in MB10 versus BB10 (p=0.026), but other behavioral tests showed no significant differences. Glial fibrillary acidic protein stains showed gliosis in arms BB10, BB30, and MB30 but not in NoRT or MB10. A secondary finding was categorically higher epilation in broad-beam arms compared with their minibeam dose counterparts. Conclusion: Our findings indicate trends that, despite the higher peak doses, proton minibeam therapy can reduce radiation side effects in shallow tissue and brain compared to proton broadbeam therapy. As the behavioral findings were mixed, confirmation studies are needed with larger numbers of animals. AAPM Research Seed Funding Grant.« less

Experimental Comparison of Knife-Edge and Multi-Parallel Slit Collimators for Prompt Gamma Imaging of Proton Pencil Beams.

PubMed

Smeets, Julien; Roellinghoff, Frauke; Janssens, Guillaume; Perali, Irene; Celani, Andrea; Fiorini, Carlo; Freud, Nicolas; Testa, Etienne; Prieels, Damien

2016-01-01

More and more camera concepts are being investigated to try and seize the opportunity of instantaneous range verification of proton therapy treatments offered by prompt gammas emitted along the proton tracks. Focusing on one-dimensional imaging with a passive collimator, the present study experimentally compared in combination with the first, clinically compatible, dedicated camera device the performances of instances of the two main options: a knife-edge slit (KES) and a multi-parallel slit (MPS) design. These two options were experimentally assessed in this specific context as they were previously demonstrated through analytical and numerical studies to allow similar performances in terms of Bragg peak retrieval precision and spatial resolution in a general context. Both collimators were prototyped according to the conclusions of Monte Carlo optimization studies under constraints of equal weight (40 mm tungsten alloy equivalent thickness) and of the specificities of the camera device under consideration (in particular 4 mm segmentation along beam axis and no time-of-flight discrimination, both of which less favorable to the MPS performance than to the KES one). Acquisitions of proton pencil beams of 100, 160, and 230 MeV in a PMMA target revealed that, in order to reach a given level of statistical precision on Bragg peak depth retrieval, the KES collimator requires only half the dose the present MPS collimator needs, making the KES collimator a preferred option for a compact camera device aimed at imaging only the Bragg peak position. On the other hand, the present MPS collimator proves more effective at retrieving the entrance of the beam in the target in the context of an extended camera device aimed at imaging the whole proton track within the patient.