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

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

WE-D-BRB-02: Proton Treatment Planning and Beam Optimization

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

Pankuch, M.

2016-06-15

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

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.

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.

LiF TLD-100 as a Dosimeter in High Energy Proton Beam Therapy-Can It Yield Accurate Results?

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

Zullo, John R.; Kudchadker, Rajat J.; Zhu, X. Ronald

In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly inmore » the distal fall-off region. All measurements were made along the central axis of an unmodulated 200-MeV proton beam from a Probeat passive beam-scattering proton accelerator (Hitachi, Ltd., Tokyo, Japan) at varying depths along the Bragg peak. Measurements were made using TLD-100 powder flat packs, placed in a virtual water slab phantom. The measurements were repeated using a parallel plate ionization chamber. The dose measurements using TLD-100 in a proton beam were accurate to within {+-}5.0% of the expected dose, previously seen in our past photon and electron measurements. The ionization chamber and the TLD relative dose measurements agreed well with each other. Absolute dose measurements using TLD agreed with ionization chamber measurements to within {+-} 3.0 cGy, for an exposure of 100 cGy. In our study, the differences in the dose measured by the ionization chamber and those measured by TLD-100 were minimal, indicating that the accuracy and precision of measurements made in the distal fall-off region of a pristine Bragg peak is within the expected range. Thus, the rapid change in stopping power ratios at the end of the range should not affect such measurements, and TLD-100 may be used with confidence as an in vivo dosimeter for proton beam therapy.« less

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

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.

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.

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.

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease.

PubMed

Savarino, Edoardo; Marabotto, Elisa; Zentilin, Patrizia; Frazzoni, Marzio; Sammito, Giorgio; Bonfanti, Daria; Sconfienza, Luca; Assandri, Lorenzo; Gemignani, Lorenzo; Malesci, Alberto; Savarino, Vincenzo

2011-07-01

Functional heartburn is defined by Rome III criteria as an endoscopy-negative condition with normal oesophageal acid exposure time, negative symptom association to acid reflux and unsatisfactory response to proton pump inhibitors. These criteria underestimated the role of non-acid reflux. To assess the contribution of impedance-pH with symptom association probability (SAP) analysis in identifying endoscopy-negative patients with reflux disease and separating them from functional heartburn. Consecutive endoscopy-negative patients treated with proton pump inhibitors (n=219) undergoing impedance-pH monitoring off-therapy were analysed. Distal acid exposure time, reflux episodes, SAP and symptomatic response to proton pump inhibitors were measured. Based on impedance-pH/SAP, 67 (31%) patients were pH+/SAP+, 6 (2%) pH+/SAP-, 83 (38%) hypersensitive oesophagus and 63 (29%) functional heartburn. According to pH-metry alone/response to proton pump inhibitors, 62 (28%) were pH+/SAP+, 11 (5%) pH+/SAP-, 61 (28%) hypersensitive oesophagus and 85 (39%) functional heartburn. In the normal-acid exposure population the contribution of impedance-pH/SAP compared to pH-metry alone/response to proton pump inhibitors in identifying patients with reflux disease and functional heartburn resulted to be 10%. In patients with abnormal-acid exposure, the contribution of impedance-pH/SAP increased by 3%. Comparing impedance-pH testing with pH-metry alone plus the response to proton pump inhibitor therapy demonstrated that the latter ones cause underestimation of reflux disease patients and overestimation of functional heartburn patients. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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 .

Malfunctions of Implantable Cardiac Devices in Patients Receiving Proton Beam Therapy: Incidence and Predictors

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

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Poenisch, Falk; Pinnix, Chelsea C.

2013-11-01

Purpose: Photon therapy has been reported to induce resets of implanted cardiac devices, but the clinical sequelae of treating patients with such devices with proton beam therapy (PBT) are not well known. We reviewed the incidence of device malfunctions among patients undergoing PBT. Methods and Materials: From March 2009 through July 2012, 42 patients with implanted cardiac implantable electronic devices (CIED; 28 pacemakers and 14 cardioverter-defibrillators) underwent 42 courses of PBT for thoracic (23, 55%), prostate (15, 36%), liver (3, 7%), or base of skull (1, 2%) tumors at a single institution. The median prescribed dose was 74 Gy (relativemore » biological effectiveness; range 46.8-87.5 Gy), and the median distance from the treatment field to the CIED was 10 cm (range 0.8-40 cm). Maximum proton and neutron doses were estimated for each treatment course. All CIEDs were checked before radiation delivery and monitored throughout treatment. Results: Median estimated peak proton and neutron doses to the CIED in all patients were 0.8 Gy (range 0.13-21 Gy) and 346 Sv (range 11-1100 mSv). Six CIED malfunctions occurred in 5 patients (2 pacemakers and 3 defibrillators). Five of these malfunctions were CIED resets, and 1 patient with a defibrillator (in a patient with a liver tumor) had an elective replacement indicator after therapy that was not influenced by radiation. The mean distance from the proton beam to the CIED among devices that reset was 7.0 cm (range 0.9-8 cm), and the mean maximum neutron dose was 655 mSv (range 330-1100 mSv). All resets occurred in patients receiving thoracic PBT and were corrected without clinical incident. The generator for the defibrillator with the elective replacement indicator message was replaced uneventfully after treatment. Conclusions: The incidence of CIED resets was about 20% among patients receiving PBT to the thorax. We recommend that PBT be avoided in pacing-dependent patients and that patients with any type of CIED receiving thoracic PBT be followed closely.« less

Modeling patterns of anatomical deformations in prostate patients undergoing radiation therapy with an endorectal balloon

NASA Astrophysics Data System (ADS)

Brion, Eliott; Richter, Christian; Macq, Benoit; Stützer, Kristin; Exner, Florian; Troost, Esther; Hölscher, Tobias; Bondar, Luiza

2017-03-01

External beam radiation therapy (EBRT) treats cancer by delivering daily fractions of radiation to a target volume. For prostate cancer, the target undergoes day-to-day variations in position, volume, and shape. For stereotactic photon and for proton EBRT, endorectal balloons (ERBs) can be used to limit variations. To date, patterns of non-rigid variations for patients with ERB have not been modeled. We extracted and modeled the patient-specific patterns of variations, using regularly acquired CT-images, non-rigid point cloud registration, and principal component analysis (PCA). For each patient, a non-rigid point-set registration method, called Coherent Point Drift, (CPD) was used to automatically generate landmark correspondences between all target shapes. To ensure accurate registrations, we tested and validated CPD by identifying parameter values leading to the smallest registration errors (surface matching error 0.13+/-0.09 mm). PCA demonstrated that 88+/-3.2% of the target motion could be explained using only 4 principal modes. The most dominant component of target motion is a squeezing and stretching in the anterior-posterior and superior-inferior directions. A PCA model of daily landmark displacements, generated using 6 to 10 CT-scans, could explain well the target motion for the CT-scans not included in the model (modeling error decreased from 1.83+/-0.8 mm for 6 CT-scans to 1.6+/-0.7 mm for 10 CT-scans). PCA modeling error was smaller than the naive approximation by the mean shape (approximation error 2.66+/-0.59 mm). Future work will investigate the use of the PCA-model to improve the accuracy of EBRT techniques that are highly susceptible to anatomical variations such as, proton therapy

LiF TLD-100 as a dosimeter in high energy proton beam therapy--can it yield accurate results?

PubMed

Zullo, John R; Kudchadker, Rajat J; Zhu, X Ronald; Sahoo, Narayan; Gillin, Michael T

2010-01-01

In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly in the distal fall-off region. All measurements were made along the central axis of an unmodulated 200-MeV proton beam from a Probeat passive beam-scattering proton accelerator (Hitachi, Ltd., Tokyo, Japan) at varying depths along the Bragg peak. Measurements were made using TLD-100 powder flat packs, placed in a virtual water slab phantom. The measurements were repeated using a parallel plate ionization chamber. The dose measurements using TLD-100 in a proton beam were accurate to within +/-5.0% of the expected dose, previously seen in our past photon and electron measurements. The ionization chamber and the TLD relative dose measurements agreed well with each other. Absolute dose measurements using TLD agreed with ionization chamber measurements to within +/- 3.0 cGy, for an exposure of 100 cGy. In our study, the differences in the dose measured by the ionization chamber and those measured by TLD-100 were minimal, indicating that the accuracy and precision of measurements made in the distal fall-off region of a pristine Bragg peak is within the expected range. Thus, the rapid change in stopping power ratios at the end of the range should not affect such measurements, and TLD-100 may be used with confidence as an in vivo dosimeter for proton beam therapy. Copyright 2010 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

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

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

[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.

SU-F-T-163: Improve Proton Therapy Efficiency: Report of a Workshop

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

Zheng, Y; Flanz, J; Mah, D

Purpose: The technology of proton therapy, especially the pencil beam scanning technique, is evolving very quickly. However, the efficiency of proton therapy seems to lag behind conventional photon therapy. The purpose of the abstract is to report on the findings of a workshop on improvement of QA, planning and treatment efficiency in proton therapy. Methods: A panel of physicists, clinicians, and vendor representatives from over 18 institutions in the United States and internationally were convened in Knoxville, Tennessee in November, 2015. The panel discussed several topics on how to improve proton therapy efficiency, including 1) lean principle and failure modemore » and effects analysis, 2) commissioning and machine QA, 3) treatment planning, optimization and evaluation, 4) patient positioning and IGRT, 5) vendor liaison and machine availability, and 6) staffing, education and training. Results: The relative time needed for machine QA, treatment planning & check in proton therapy was found to range from 1 to 2.5 times of that in photon therapy. Current status in proton QA, planning and treatment was assessed. Key areas for efficiency improvement, such as elimination of unnecessary QA items or steps and development of efficient software or hardware tools, were identified. A white paper to summarize our findings is being written. Conclusion: It is critical to improve efficiency by developing reliable proton beam lines, efficient software tools on treatment planning, optimization and evaluation, and dedicated proton QA device. Conscious efforts and collaborations from both industry leaders and proton therapy centers are needed to achieve this goal and further advance the technology of proton therapy.« less

Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Sengbusch, Evan R.

Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing, beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy.

PubMed

Shiraishi, Yutaka; Fang, Penny; Xu, Cai; Song, Juhee; Krishnan, Sunil; Koay, Eugene J; Mehran, Reza J; Hofstetter, Wayne L; Blum-Murphy, Mariela; Ajani, Jaffer A; Komaki, Ritsuko; Minsky, Bruce; Mohan, Radhe; Hsu, Charles C; Hobbs, Brian P; Lin, Steven H

2017-12-13

Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P < 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16-0.52; P < 0.0001). PBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

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.

Intraoperative Localization of Tantalum Markers for Proton Beam Radiation of Choroidal Melanoma by an Opto-Electronic Navigation System: A Novel Technique

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

Amstutz, Christoph A., E-mail: christoph.amstutz@usz.ch; Bechrakis, Nikolaos E.; Foerster, Michael H.

2012-03-15

Purpose: External beam proton radiation therapy has been used since 1975 to treat choroidal melanoma. For tumor location determination during proton radiation treatment, surgical tantalum clips are registered with image data. This report introduces the intraoperative application of an opto-electronic navigation system to determine with high precision the position of the tantalum markers and their spatial relationship to the tumor and anatomical landmarks. The application of the technique in the first 4 patients is described. Methods and Materials: A navigated reference base was attached noninvasively to the eye, and a navigated pointer device was used to record the spatial positionmore » of the tantalum markers, the tumor, and anatomical landmarks. Measurement accuracy was assessed on ex vivo porcine eye specimen by repetitive recording of the tantalum marker positions. The method was applied intraoperatively on 4 patients undergoing routine tantalum clip surgery. The spatial position information delivered by the navigation system was compared to the geometric data generated by the EYEPLAN software. Results: In the ex vivo experiments, the maximum repetition error was 0.34 mm. For the intraoperative application, the root mean square error of paired-points matching of the marker positions from the navigation system and from the EYEPLAN software was 0.701-1.25 mm. Conclusions: Navigation systems are a feasible tool for accurate localization of tantalum markers and anatomic landmarks. They can provide additional geometric information, and therefore have the potential to increase the reliability and accuracy of external beam proton radiation therapy for choroidal melanoma.« less

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

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients: a nationwide register-based study in Denmark.

PubMed

Lødrup, A; Pottegård, A; Hallas, J; Bytzer, P

2015-07-01

Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. To determine the use of proton pump inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients, the Danish National Prescription Register, and the Danish Person Register. The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery to 64.9% 1 year before. The probability for inadequate dosing 1 year before surgery (<180 DDD) was significantly increased for younger patients, patients operated in the period 2000-2003, patients who had not undergone pre-surgical manometry, pH- or impedance monitoring, and patients who had not redeemed prescriptions on NSAID or anti-platelet drugs. Compliance with medical therapy should be evaluated thoroughly before planning anti-reflux surgery, as a high proportion of patients receive inadequate dosing of acid-suppressive therapy prior to the operation. © 2015 John Wiley & Sons Ltd.

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.

Loss of H2 and CO from protonated aldehydes in electrospray ionization mass spectrometry.

PubMed

Neta, Pedatsur; Simón-Manso, Yamil; Liang, Yuxue; Stein, Stephen E

2014-09-15

Electrospray ionization mass spectrometry (ESI-MS) of many protonated aldehydes shows loss of CO as a major fragmentation pathway. However, we find that certain aldehydes undergo loss of H2 followed by reaction with water in the collision cell. This complicates interpretation of tandem mass (MS/MS) spectra and affects multiple reaction monitoring (MRM) results. 3-Formylchromone and other aldehydes were dissolved in acetonitrile/water/formic acid and studied by ESI-MS to record their MS(2) and MS(n) spectra in several mass spectrometers (QqQ, QTOF, ion trap (IT), and Orbitrap HCD). Certain product ions were found to react with water and the rate of reaction was determined in the IT instrument using zero collision energy and variable activation times. Theoretical calculations were performed to help with the interpretation of the fragmentation mechanism. Protonated 3-formylchromones and 3-formylcoumarins undergo loss of H2 as a major fragmentation route to yield a ketene cation, which reacts with water to form a protonated carboxylic acid. In general, protonated aldehydes which contain a vicinal group that forms a hydrogen bridge with the formyl group undergo significant loss of H2. Subsequent losses of CO and C3O are also observed. Theoretical calculations suggest mechanistic details for these losses. Loss of H2 is a major fragmentation channel for protonated 3-formychromones and certain other aldehydes and it is followed by reaction with water to produce a protonated carboxylic acid, which undergoes subsequent fragmentation. This presents a problem for reference libraries and raises concerns about MRM results. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.

"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.

Practical Radiobiology for Proton Therapy Planning

NASA Astrophysics Data System (ADS)

Jones, Bleddyn

2017-12-01

Practical Radiobiology for Proton Therapy Planning covers the principles, advantages and potential pitfalls that occur in proton therapy, especially its radiobiological modelling applications. This book is intended to educate, inform and to stimulate further research questions. Additionally, it will help proton therapy centres when designing new treatments or when unintended errors or delays occur. The clear descriptions of useful equations for high LET particle beam applications, worked examples of many important clinical situations, and discussion of how proton therapy may be optimized are all important features of the text. This important book blends the relevant physics, biology and medical aspects of this multidisciplinary subject. Part of Series in Physics and Engineering in Medicine and Biology.

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

Proton therapy - Present and future.

PubMed

Mohan, Radhe; Grosshans, David

2017-01-15

In principle, proton therapy offers a substantial clinical advantage over conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses and greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life. Protons, accelerated to therapeutic energies ranging from 70 to 250MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initial thin beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanical means to treat the patients with "passively-scattered proton therapy" (PSPT) or using magnetic scanning of thin "beamlets" of protons of a sequence of initial energies. The latter technique can be used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton modality. Despite the high potential of proton therapy, the clinical evidence supporting the broad use of protons is mixed. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Although promising results have been and continue to be reported for many other types of cancers, they are based on small studies. Considering the high cost of establishing and operating proton therapy centers, questions have been raised about their cost effectiveness. General consensus is that there is a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to unequivocally demonstrate the advantage of protons. Treatment planning and plan evaluation of PSPT and IMPT require special considerations compared to the processes used for photon treatment planning. The differences in techniques arise from the unique physical properties of protons but are also necessary because of the greater vulnerability of protons to uncertainties, especially from inter- and intra-fractional variations in anatomy. These factors must be considered in designing as well as evaluating treatment plans. In addition to anatomy variations, other sources of uncertainty in dose delivered to the patient include the approximations and assumptions of models used for computing dose distributions for planning of treatments. Furthermore, the relative biological effectiveness (RBE) of protons is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of the energy of protons, dose per fraction, tissue and cell type, end point, etc. These uncertainties, approximations and current technological limitations of proton therapy may limit the achievement of its true potential. Ongoing research is aimed at better understanding the consequences of the various uncertainties on proton therapy and reducing the uncertainties through image-guidance, adaptive radiotherapy, further study of biological properties of protons and the development of novel dose computation and optimization methods. However, residual uncertainties will remain in spite of the best efforts. To increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented. We assert that, with such research, proton therapy will be a commonly applied radiotherapy modality for most types of solid cancers in the near future. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Comprehensive analysis of proton range uncertainties related to patient stopping-power-ratio estimation using the stoichiometric calibration

PubMed Central

Yang, M; Zhu, X R; Park, PC; Titt, Uwe; Mohan, R; Virshup, G; Clayton, J; Dong, L

2012-01-01

The purpose of this study was to analyze factors affecting proton stopping-power-ratio (SPR) estimations and range uncertainties in proton therapy planning using the standard stoichiometric calibration. The SPR uncertainties were grouped into five categories according to their origins and then estimated based on previously published reports or measurements. For the first time, the impact of tissue composition variations on SPR estimation was assessed and the uncertainty estimates of each category were determined for low-density (lung), soft, and high-density (bone) tissues. A composite, 95th percentile water-equivalent-thickness uncertainty was calculated from multiple beam directions in 15 patients with various types of cancer undergoing proton therapy. The SPR uncertainties (1σ) were quite different (ranging from 1.6% to 5.0%) in different tissue groups, although the final combined uncertainty (95th percentile) for different treatment sites was fairly consistent at 3.0–3.4%, primarily because soft tissue is the dominant tissue type in human body. The dominant contributing factor for uncertainties in soft tissues was the degeneracy of Hounsfield Numbers in the presence of tissue composition variations. To reduce the overall uncertainties in SPR estimation, the use of dual-energy computed tomography is suggested. The values recommended in this study based on typical treatment sites and a small group of patients roughly agree with the commonly referenced value (3.5%) used for margin design. By using tissue-specific range uncertainties, one could estimate the beam-specific range margin by accounting for different types and amounts of tissues along a beam, which may allow for customization of range uncertainty for each beam direction. PMID:22678123

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

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.

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.

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.

Preliminary test of the MONDO project secondary fast and ultrafast neutrons tracker response using protons and MIP particles

NASA Astrophysics Data System (ADS)

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

2018-04-01

The risk of developing a second malignant cancer as a late time consequence of undergoing a treatment, is one of the main concerns in particle therapy (PT). Since neutrons can release a significant dose far away from the tumour region, a precise characterisation of their production point, kinetic energy and abundance is eagerly needed. The treatment planning system (TPS) software that predicts the normal tissue toxicity in the target region and the risk of late complications in the whole body is currently based on the poorly known production cross-sections and will greatly benefit from improved precision double differential measurements. The MONDO (MOnitor for Neutron Dose in hadrOntherapy) project aims to build an ultrafast neutron tracker that could be used to characterise the production of secondary neutrons with energies in the 20–400 MeV range. The neutron tracking will proceed via the detection of recoil protons produced in two consecutive (n, p) elastic scattering interactions. The MONDO detector consists of a 10 × 10 × 20 cm3 matrix of thin scintillating fibres, arranged in orthogonally oriented layers. A compact read-out sensor with single photon detection capabilities employing the CMOS SPAD technology has been developed in collaboration with Fondazione Bruno Kessler (FBK). The detector will be completed by the end of 2018. A 4 × 4 × 4.8 cm3 prototype has been built using 250 μ m thick scintillating fibres of squared section and was tested using a proton beam and minimum ionising particles. In this contribution we present the experimental results related to the prototype test performed with a proton beam at the Proton Therapy Centre of the Trento Hospital (PTC) in May 2017. The results are compared with the results of a Monte Carlo simulation performed with the FLUKA software.

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.

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.

Current and future treatment of chest pain of presumed esophageal origin.

PubMed

Schmulson, Max J; Valdovinos, Miguel Angel

2004-03-01

Patients with chest pain of presumed esophageal origin should be reassured and should undergo an esophageal manometry study. In patients with spastic esophageal disorders, a trial with calcium channel blockers or low-dose antidepressants used as visceral analgesics is the best approach. Inpatients with non GERD-related, nonspastic esophageal motility disorder, low-dose antidepressants seem reasonable. Anxiolytics are useful in patients with panic disorders, and psychological interventions (eg, cognitive-behavioral therapy) are also valuable, mainly in patients in whom reassurance is not sufficient to avoid the misinterpretation of their symptoms. In the future, visceral sensitivity modifying agents such as serotoninergic agonists or antagonists may become the cornerstone of therapy in patients with chest pain of presumed esophageal origin. Combinations of different approaches, such as proton pump inhibitors and psychotropic or antinociceptive agents, should also be evaluated in clinical trials.

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

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.

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

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.

Human exposure to large solar particle events in space

NASA Technical Reports Server (NTRS)

Townsend, L. W.; Wilson, J. W.; Shinn, J. L.; Curtis, S. B.

1992-01-01

Whenever energetic solar protons produced by solar particle events traverse bulk matter, they undergo various nuclear and atomic collision processes which significantly alter the physical characteristics and biologically important properties of their transported radiation fields. These physical interactions and their effect on the resulting radiation field within matter are described within the context of a recently developed deterministic, coupled neutron-proton space radiation transport computer code (BRYNTRN). Using this computer code, estimates of human exposure in interplanetary space, behind nominal (2 g/sq cm) and storm shelter (20 g/sq cm) thicknesses of aluminum shielding, are made for the large solar proton event of August 1972. Included in these calculations are estimates of cumulative exposures to the skin, ocular lens, and bone marrow as a function of time during the event. Risk assessment in terms of absorbed dose and dose equivalent is discussed for these organs. Also presented are estimates of organ exposures for hypothetical, worst-case flare scenarios. The rate of dose equivalent accumulation places this situation in an interesting region of dose rate between the very low values of usual concern in terrestrial radiation environments and the high-dose-rate values prevalent in radiation therapy.

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.

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.

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

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

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.

Antiplatelet drug interactions with proton pump inhibitors

PubMed Central

Scott, Stuart A; Obeng, Aniwaa Owusu; Hulot, Jean-Sébastien

2014-01-01

Introduction Non-aspirin antiplatelet agents (e.g., clopidogrel, prasugrel, ticagrelor) are commonly prescribed for the prevention of recurrent cardiovascular events among patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI). In addition, combination therapy with proton pump inhibitors (PPIs) is often recommended to attenuate gastrointestinal bleeding risk, particularly during dual antiplatelet therapy (DAPT) with clopidogrel and aspirin. Importantly, a pharmacological interaction between clopidogrel and some PPIs has been proposed based on mutual CYP450-dependent metabolism, but available evidence is inconsistent. Areas covered This article provides an overview of the currently approved antiplatelet agents and PPIs, including their metabolic pathways. Additionally, the CYP450 isoenzyme at the center of the drug interaction, CYP2C19, is described in detail, and the available evidence on both the potential pharmacological interaction and influence on clinical outcomes are summarized and evaluated. Expert opinion Although concomitant DAPT and PPI use reduces clopidogrel active metabolite levels and ex vivo-measured platelet inhibition, the influence of the drug interaction on clinical outcomes has been conflicting and largely reported from non-randomized observational studies. Despite this inconsistency, a clinically important interaction cannot be definitively excluded, particularly among patient subgroups with higher overall cardiovascular risk and potentially among CYP2C19 loss-of-function allele carriers. PMID:24205916

Adverse drug reactions due to drug-drug interactions with proton pump inhibitors: assessment of systematic reviews with AMSTAR method.

PubMed

Yucel, Emre; Sancar, Mesut; Yucel, Aylin; Okuyan, Betul

2016-01-01

Many systematic reviews resulted in claims on drug-drug interactions (DDIs) with proton pump inhibitors (PPIs). Such a large number begs for consensus on the clinical significance of findings. We critically evaluated the safety of PPI use with respect to DDIs with a meta-review of systematic reviews published between 1978 and 2015. We assessed the evidence by their reliability, repeatability, transparency, and objectivity according to the Assessment of Multiple Systematic Reviews (AMSTAR) criteria. Clinicians must assess risks for each PPI for certain comorbid conditions. DDIs don't substantiate class effect for PPIs; each PPI could induce unique DDIs. Concomitant use of PPIs with thienopyridines (e.g. clopidogrel) could be justified in patients without strong affinity to cytochrome CYP2C19 and with high risk of bleeding (e.g. patients with prior upper gastrointestinal bleeding, Helicobacter pylori infection, advanced age, steroid treatment, and nonsteroidal anti-inflammatory drug use). DDIs could occur in an AIDS subpopulation treated with highly active antiretroviral therapy (HAART). DDIs exist for cancer patients undergoing targeted therapy. Hypomagnesemia could increase in the setting of advanced age and polypharmacy. Omeprazole poses high risks owing to its pharmacokinetic DDI profile. Future systematic reviews should incorporate these additional risks for better clinical guidance.

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

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

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

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.

The Pain System in Oesophageal Disorders: Mechanisms, Clinical Characteristics, and Treatment

PubMed Central

Lottrup, Christian; Olesen, Søren Schou; Drewes, Asbjørn Mohr

2011-01-01

Pain is common in gastroenterology. This review aims at giving an overview of pain mechanisms, clinical features, and treatment options in oesophageal disorders. The oesophagus has sensory receptors specific for different stimuli. Painful stimuli are encoded by nociceptors and communicated via afferent nerves to the central nervous system. The pain stimulus is further processed and modulated in specific pain centres in the brain, which may undergo plastic alterations. Hence, tissue inflammation and long-term exposure to pain can cause sensitisation and hypersensitivity. Oesophageal sensitivity can be evaluated ,for example, with the oesophageal multimodal probe. Treatment should target the cause of the patient's symptoms. In gastro-oesophageal reflux diseases, proton pump inhibitors are the primary treatment option, surgery being reserved for patients with severe disease resistant to drug therapy. Functional oesophageal disorders are treated with analgesics, antidepressants, and psychological therapy. Lifestyle changes are another option with less documentation. PMID:21826137

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.

[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.

SU-E-T-115: Dose Perturbation Study of Self-Expandable Metal and Polyester Esophageal Stents in Proton Therapy Beams

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

Lee, S; Li, Z; Jalaj, S

2014-06-01

Purpose: This work investigates dose perturbations due to Self-expandable metal and polyester esophageal stents undergoing proton radiotherapy for esophageal cancer. Methods: Five commercially available esophageal stents made of nitinol (Evolution, Wallflex and Ultraflex), stainless steel (Z-Stent) and polyester (Polyflex) were tested. Radiochromic film (GafChromic EBT3 film, Ashland, Covington, KY) wrapped around a stent and a 12cc syringe was irradiated with 2CGE (Cobalt Gray Equivalent) of proton beam in a custom fabricated acrylic phantom. An air-hollow syringe simulates the esophagus. Results: The Z-stent created the largest dose perturbations ranges from -14.5% to 6.1% due to the steel composition. The WallFlex, Evolutionmore » and Ultraflex stents produced the dose perturbation ranges of (−9.2%∼8.6%), (−6.8%∼5.7%) and (−6.2%∼6.2%), respectively. The PolyFlex stent contains the radiopaque tungsten markers located top, middle and bottom portions. When the focal cold spots induced by the markers were excluded in the analysis, the dose perturbation range was changed from (−11.6%∼6.4%) to (−0.6%∼5.0%). Conclusion: The magnitude of dose perturbation is related to material of a metallic stent. The non-metallic stent such as PolyFlex shows relatively lower dose perturbation than metallic stents except a radiopaque marker region. Overall Evolution and Ultraflex stent appear to be less dose perturbations. The largest dose perturbations (cold spots) were located at both edges of stents in distal area for the single proton beam irradiation study. The analysis of more than two proton beam which is more typical clinical beam arrangement would be necessary to minimize the doe perturbation effect in proton ratiotherapy.« less

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.

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-F-J-122: Rectal Sparing Reproducibility in Prostate Cancer Patients Treated with Hydrogel Spacer and Proton Therapy

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

Hedrick, S; Robison, B; Blakey, M

2016-06-15

Purpose: Rectal hydrogel spacer has been shown to improve rectal sparing in prostate radiotherapy. The purpose of this study was to determine the reproducibility of rectal sparing throughout treatment in patients undergoing proton therapy. Methods: At our facility, prostate cancer patients are treated with pencil beam scanning proton therapy, utilizing an endorectal balloon (ERB) or rectal spacer hydrogel (Gel) “SpaceOAR” implant. All patients were treated with a full bladder and empty rectum (low residue diet and stool softeners). A quality assurance CT (QACT) was performed periodically throughout treatment to ensure rectal filling consistency and sparing in 41 patients treated withmore » Gel. The treatment planning (TP) dose was calculated on each QACT and the rectum V90%, V75%, V65%, V50%, and V40% were recorded. QACT scans were acquired on day 0, week 1, week 3, and week 5. Results: 144 QACT scans were analyzed, each patient receiving 3–4 QACTs. Rectum V90% was within +/−1% of the TP dose in 70% of the QACTs and within +/−5% in 95% of scans. From previous data analyses, our ERB rectum V90% average is 6%. This value was used as an upper threshold for the Gel QACT analysis. 5 of the 41 patients (12%), corresponding to 7 QACTs, had a rectum V90% that exceeded 6% on one or more QACTs. However, the average rectal V90% measured over multiple QACTs never exceeded 6%. 55% of the QACTs had a rectum volume within 5cc of the TPCT volume, 68% were within 10cc. Conclusion: In this study, we have shown that a majority of our prostate patients can maintain consistent rectal sparing when treated with a hydrogel spacer. QACT rectal V90% exceeding our threshold was most often related to increased rectal filling and gas, which was addressed with improved dietary compliance and the intensification of stool softeners or laxatives.« less

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.

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.

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

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

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.

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

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.

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

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

TU-AB-BRC-09: Fast Dose-Averaged LET and Biological Dose Calculations for Proton Therapy Using Graphics Cards

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

Wan, H; Tseung, Chan; Beltran, C

Purpose: To demonstrate fast and accurate Monte Carlo (MC) calculations of proton dose-averaged linear energy transfer (LETd) and biological dose (BD) on a Graphics Processing Unit (GPU) card. Methods: A previously validated GPU-based MC simulation of proton transport was used to rapidly generate LETd distributions for proton treatment plans. Since this MC handles proton-nuclei interactions on an event-by-event using a Bertini intranuclear cascade-evaporation model, secondary protons were taken into account. The smaller contributions of secondary neutrons and recoil nuclei were ignored. Recent work has shown that LETd values are sensitive to the scoring method. The GPU-based LETd calculations were verifiedmore » by comparing with a TOPAS custom scorer that uses tabulated stopping powers, following recommendations by other authors. Comparisons were made for prostate and head-and-neck patients. A python script is used to convert the MC-generated LETd distributions to BD using a variety of published linear quadratic models, and to export the BD in DICOM format for subsequent evaluation. Results: Very good agreement is obtained between TOPAS and our GPU MC. Given a complex head-and-neck plan with 1 mm voxel spacing, the physical dose, LETd and BD calculations for 10{sup 8} proton histories can be completed in ∼5 minutes using a NVIDIA Titan X card. The rapid turnover means that MC feedback can be obtained on dosimetric plan accuracy as well as BD hotspot locations, particularly in regards to their proximity to critical structures. In our institution the GPU MC-generated dose, LETd and BD maps are used to assess plan quality for all patients undergoing treatment. Conclusion: Fast and accurate MC-based LETd calculations can be performed on the GPU. The resulting BD maps provide valuable feedback during treatment plan review. Partially funded by Varian Medical Systems.« 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…

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

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

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.

Utility of an Australasian registry for children undergoing radiation treatment.

PubMed

Ahern, Verity

2014-12-01

The aim of this study was to evaluate the utility of an Australasian registry ('the Registry') for children undergoing radiation treatment (RT). Children under the age of 16 years who received a course of radiation between January 1997 and December 2010 and were enrolled on the Registry form the subjects of this study. A total of 2232 courses of RT were delivered, predominantly with radical intent (87%). Registrations fluctuated over time, but around one-half of children diagnosed with cancer undergo a course of RT. The most prevalent age range at time of RT was 10-15 years, and the most common diagnoses were central nervous system tumours (34%) and acute lymphoblastic leukaemia (20%). The Registry provides a reflection of the patterns of care of children undergoing RT in Australia and a mechanism for determining the resources necessary to manage children by RT (human, facilities and emerging technologies, such as proton therapy). It lacks the detail to provide information on radiotherapy quality and disease outcomes which should be the subject of separate audit studies. The utility of the Registry has been hampered by its voluntary nature and varying needs for consent. Completion of registry forms is a logical requirement for inclusion in the definition of a subspecialist in paediatric radiation oncology. © 2014 The Royal Australian and New Zealand College of Radiologists.

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.

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

Diagnosis and treatment of gastroesophageal reflux disease

PubMed Central

Badillo, Raul; Francis, Dawn

2014-01-01

Gastroesophageal reflux disease (GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical, atypical and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms, these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations, further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis, peptic stricture, Barrett’s esophagus, esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification, medical therapy and surgical therapy. Lifestyle modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids, histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy, others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gastroesophageal reflux disease. PMID:25133039

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.

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.

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.

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.

Dosimetric investigation of proton therapy on CT-based patient data using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Chongsan, T.; Liamsuwan, T.; Tangboonduangjit, P.

2016-03-01

The aim of radiotherapy is to deliver high radiation dose to the tumor with low radiation dose to healthy tissues. Protons have Bragg peaks that give high radiation dose to the tumor but low exit dose or dose tail. Therefore, proton therapy is promising for treating deep- seated tumors and tumors locating close to organs at risk. Moreover, the physical characteristic of protons is suitable for treating cancer in pediatric patients. This work developed a computational platform for calculating proton dose distribution using the Monte Carlo (MC) technique and patient's anatomical data. The studied case is a pediatric patient with a primary brain tumor. PHITS will be used for MC simulation. Therefore, patient-specific CT-DICOM files were converted to the PHITS input. A MATLAB optimization program was developed to create a beam delivery control file for this study. The optimization program requires the proton beam data. All these data were calculated in this work using analytical formulas and the calculation accuracy was tested, before the beam delivery control file is used for MC simulation. This study will be useful for researchers aiming to investigate proton dose distribution in patients but do not have access to proton therapy machines.

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-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.

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.

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.

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.

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

Mandapaka, A; Ghebremedhin, A; Patyal, B

Purpose: Patients who undergo n-BCA glue embolization as part of treatment for AVMs are later referred for proton therapy. Knowing the relative stopping power of the glue accurately allows us to perform accurate dose calculations. In this study we experimentally determine the relative stopping power of an n-BCA mixture in a 126 MeV and 149.6 MeV proton beams. Methods: One unit of the TRUFILL™ n-BCA liquid embolic system consists of 1g unit of n-BCA, 1g unit of Tantalum powder and one 10mL vial of Ethiodized oil. The physician mixed 3:1 Ethiodized oil to n-BCA. Five units (20cc) of the n-BCAmore » liquid embolic glue were prepared and placed in a 6cm x 3cm x3cm Lucite container. The container was placed in front of a water tank in the proton beam path. A diamond detector (active volume 0.004mm3) was used to measure distal edge of depth dose of a modulated 126 MeV proton beam collimated using a 3cm brass aperture. The procedure was repeated with a container carrying the same amount of water placed in front of the water tank. The difference in the depth dose measured with glue and with water was used to determine the relative stopping power of the glue. The same determination was done earlier at 149.6 MeV using a different smaller sample (4cc) of n-BCA. Results: The relative stopping power of this particular n-BCA mixture was determined to be 1.06 at both 126 MeV and 149.6 MeV. We are working on obtaining the composition data of the n-BCA glue so we can perform Monte Carlo calculations. Conclusion: Accurate value of the stopping power of the n-BCA glue in the proton beam was determined to be 1.06. It will improve the accuracy of dose calculations in proton radiosurgery procedures on AVM patients with n-BCA embolization.« 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.

A comparison of 30-day versus 90-day proton pump inhibitor therapy in prevention of marginal ulcers after laparoscopic Roux-en-Y gastric bypass.

PubMed

Kang, Xian; Zurita-Macias, Luis; Hong, Dennis; Cadeddu, Margherita; Anvari, Mehran; Gmora, Scott

2016-06-01

Marginal ulceration is one of the most common complications after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Proton pump inhibitors (PPIs) are commonly administered to decrease the incidence of marginal ulcer development. We examine the differential impact of employing a 30-day versus 90-day postoperative PPI regimen on the development of marginal ulceration after LRYGB. University hospital. A retrospective cohort design was used to study all patients undergoing LRYGB at a single, high-volume bariatric center in Hamilton, Ontario, Canada. Three years previously, the duration of postoperative PPI administration was increased at our center from 30 to 90 days. Diagnosis of marginal ulceration was confirmed by upper endoscopy in patients presenting with epigastric pain and a clinical history suggestive of marginal ulceration. A χ(2) test of independence was performed to examine incidence of marginal ulceration and PPI duration. A total of 1016 patients underwent LRYGB at our center between January 2009 and January 2013. No differences in baseline characteristics were observed between groups. Of the 1016 patients followed, 614 received 30 days of PPI therapy and 402 received 90 days of PPI therapy. The incidence of marginal ulceration after LRYGB decreased significantly (P<.05) among patients receiving daily PPI for 90 days (n = 26, 6.5%) compared with those receiving PPI for 30 days (n = 76, 12.4%). This study suggests a significant benefit to longer duration prophylactic PPI administration after gastric bypass surgery to minimize the risk of symptomatic marginal ulceration. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

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

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.

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.

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

SU-E-T-457: Impact of Interfractional Variations On Anterior Vs. Lateral-Field Proton Therapy of Prostate Cancer

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

Moteabbed, M; Trofimov, A; Sharp, G C

2015-06-15

Purpose: To investigate the effects of interfractional anatomy and setup variations on plans with anterior-oblique vs. lateral beams for prostate cancer pencil beam scanning (PBS) and passive scattered (PS) proton therapy. Methods: Six patients with low/intermediate risk prostate cancer treated with PS proton therapy at our institution were selected. All patients underwent weekly verification CT scans. Implanted fiducials were used for localization, and endorectal balloons for prostate immobilization. New PBS plans with lateral beams, as well as PBS and PS plans with anterior-oblique beams (±35 deg) were created. PBS plans used two different spot sizes: ∼10mm (large) and ∼5mm (medium)more » sigma at 25cm range and optimized as single-field-uniform-dose with ∼8% non-uniformity. No range uncertainty margins were applied in PBS plans to maximize rectal sparing. Field-specific apertures were used when planning with large spots to sharpen the penumbrae. The planned dose was recomputed on each weekly CT with fiducials aligned to the simulation CT, scaled and accumulated via deformable image registration. Results: The dose volume analysis showed that although difference between planned and accumulated dose remains negligible for plans with conventional lateral beams using both PS and PBS, this is not the case for plans with anterior beams. The target coverage in anterior plans was largely degraded due to the variations in the beam path length and the absence of range margins. The average prostate D95 was reduced by 7.5/15.9% (using PS/PBS) after accumulation for anterior plans, compared with 0/0.4% for lateral plans. The average mean dose in organs-at-risk decreased by 1% for lateral and 2% for anterior plans, similarly for PS and PBS. Spot size did not affect the dose changes. Conclusion: Prostate plans using anterior beams may undergo clinically relevant interfractional dose degradation. Corrective strategies guided by in-vivo range measurements should be studied before clinical application of this technique.« 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-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.

Light-driven, proton-controlled, catalytic aerobic C-H oxidation mediated by a Mn(III) porphyrinoid complex.

PubMed

Neu, Heather M; Jung, Jieun; Baglia, Regina A; Siegler, Maxime A; Ohkubo, Kei; Fukuzumi, Shunichi; Goldberg, David P

2015-04-15

The visible light-driven, catalytic aerobic oxidation of benzylic C-H bonds was mediated by a Mn(III) corrolazine complex. To achieve catalytic turnovers, a strict selective requirement for the addition of protons was established. The resting state of the catalyst was unambiguously characterized by X-ray diffraction as [Mn(III)(H2O)(TBP8Cz(H))](+), in which a single, remote site on the ligand is protonated. If two remote sites are protonated, however, reactivity with O2 is shut down. Spectroscopic methods revealed that the related Mn(V)(O) complex is also protonated at the same remote site at -60 °C, but undergoes valence tautomerization upon warming.

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.

Current status of gastroesophageal reflux disease : diagnosis and treatment.

PubMed

Chuang, Tang-Wei; Chen, Shou-Chien; Chen, Kow-Tong

2017-01-01

The aim of this study was to explore the recent advances in diagnosis and treatment of gastroesophageal reflux disease (GERD). Previous studies were searched using the terms "gastroesophageal reflux disease" and "diagnosis" or "treatment" in Medline and Pubmed. Articles that were not published in the English language, manuscripts without an abstract, reviews, meta-analysis, and opinion articles were excluded from the review. After a preliminary screening, all of the articles were reviewed and synthesized to provide an overview of the contemporary approaches to GERD. GERD has a variety of symptomatic manifestations, which can be grouped into typical, atypical and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of other alarming symptoms, these symptoms allow one to make a presumptive diagnosis of GERD and initiate empiric therapy. GERD-associated complications include erosive esophagitis, peptic stricture, Barrett's esophagus, esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modifications, medical and surgical therapy. Medical therapy involves acid suppression, which can be achieved with antacids, histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy, others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The management of this disease requires a complex approach. Maintenance therapy of GERD after using anti-secretory drugs should be continuously monitored. © Acta Gastro-Enterologica Belgica.

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.

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

Beltran, C; Kamal, H

Purpose: To provide a multicriteria optimization algorithm for intensity modulated radiation therapy using pencil proton beam scanning. Methods: Intensity modulated radiation therapy using pencil proton beam scanning requires efficient optimization algorithms to overcome the uncertainties in the Bragg peaks locations. This work is focused on optimization algorithms that are based on Monte Carlo simulation of the treatment planning and use the weights and the dose volume histogram (DVH) control points to steer toward desired plans. The proton beam treatment planning process based on single objective optimization (representing a weighted sum of multiple objectives) usually leads to time-consuming iterations involving treatmentmore » planning team members. We proved a time efficient multicriteria optimization algorithm that is developed to run on NVIDIA GPU (Graphical Processing Units) cluster. The multicriteria optimization algorithm running time benefits from up-sampling of the CT voxel size of the calculations without loss of fidelity. Results: We will present preliminary results of Multicriteria optimization for intensity modulated proton therapy based on DVH control points. The results will show optimization results of a phantom case and a brain tumor case. Conclusion: The multicriteria optimization of the intensity modulated radiation therapy using pencil proton beam scanning provides a novel tool for treatment planning. Work support by a grant from Varian Inc.« less

Analysis of Giant-nucleated Cell Formation Following X-ray and Proton Irradiations

NASA Astrophysics Data System (ADS)

Almahwasi, Ashraf Abdu

Radiation-induced genetic instability has been observed in survivors of irradiated cancerous and normal cells in vitro and in vivo and has been determined in different forms, such as delayed cell death, chromosomal aberration or mutation. A well defined and characterized normal human-diploid AG1522 fibroblast cell line was used to study giant-nucleated cell (GCs) formation as the ultimate endpoint of this research. The average nuclear cross-sectional areas of the AG1522 cells were measured in mum2. The doubling time required by the AG1522 cells to divide was measured. The potential toxicity of the Hoechst dye at a working concentration on the live AG1522 cells was assessed. The yield of giant cells was determined at 7, 14 and 21 days after exposure to equivalent clinical doses of 0.2, 1 or 2 Gy of X-ray or proton irradiation. Significant differences were found to exist between X-ray or proton irradiation when compared with sham-irradiated control populations. The frequency of GCs induced by X-rays was also compared to those formed in proton irradiated cultures. The results confirm that 1 Gy X-rays are shown to induce higher rates of mitotically arrested GCs, increasing continually over time up to 21 days post-irradiation. The yield of GCs was significantly greater (10%) compared to those formed in proton populations (2%) 21 days postirradiation. The GCs can undergo a prolonged mitotic arrest that significantly increases the length of cell cycle. The arrest of GCs at the mitotic phase for longer periods of time might be indicative of a strategy for cell survival, as it increases the time available for DNA repair and enables an alternative route to division for the cells. However, the reduction in their formation 21 days after both types of radiation might favour GCs formation, ultimately contributing to carcinogenesis or cancer therapy resistance. The X-ray experiments revealed a dose-dependent increase in the GCs up to 14 days after irradiation. Although the proton irradiation was less efficient in producing GCs, their frequency was elevated in a dose-dependent manner 7 days after irradiation, with persistent expression of nuclear deformity as an indicator of genetic instability. In addition to the quantification of the GCs, the proliferation of a small fraction of giant cells formed at 14 days after 0.2 Gy of proton irradiation was observed to divide into asymmetrical, normal-sized daughter cells. These results might have important implications in evaluating risk estimates, or could act as a potential radioprotective assay for a dose-limiting parameter for delayed effects in healthy tissues during radiation therapy treatment.

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

[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.

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

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.

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.

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.

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.

Reaction Mechanism of Mycobacterium Tuberculosis Glutamine Synthetase Using Quantum Mechanics/Molecular Mechanics Calculations.

PubMed

Moreira, Cátia; Ramos, Maria J; Fernandes, Pedro Alexandrino

2016-06-27

This paper is devoted to the understanding of the reaction mechanism of mycobacterium tuberculosis glutamine synthetase (mtGS) with atomic detail, using computational quantum mechanics/molecular mechanics (QM/MM) methods at the ONIOM M06-D3/6-311++G(2d,2p):ff99SB//B3LYP/6-31G(d):ff99SB level of theory. The complete reaction undergoes a three-step mechanism: the spontaneous transfer of phosphate from ATP to glutamate upon ammonium binding (ammonium quickly loses a proton to Asp54), the attack of ammonia on phosphorylated glutamate (yielding protonated glutamine), and the deprotonation of glutamine by the leaving phosphate. This exothermic reaction has an activation free energy of 21.5 kcal mol(-1) , which is consistent with that described for Escherichia coli glutamine synthetase (15-17 kcal mol(-1) ). The participating active site residues have been identified and their role and energy contributions clarified. This study provides an insightful atomic description of the biosynthetic reaction that takes place in this enzyme, opening doors for more accurate studies for developing new anti-tuberculosis therapies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

WE-FG-BRB-04: RBEs for Human Lung Cancer Cells Exposed to Protons and Heavier Ions: Implications for Clinical Use of Charged Particles in Cancer Therapy

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

Held, K.

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

WE-FG-BRB-01: Clinical Significance of RBE Variations in Proton Therapy

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

Paganetti, H.

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

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

[18F]-Fluoromisonidazole Positron Emission Tomography/Computed Tomography Visualization of Tumor Hypoxia in Patients With Chordoma of the Mobile and Sacrococcygeal Spine

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

Cheney, Matthew D., E-mail: mcheney@lroc.harvard.edu; Chen, Yen-Lin; Lim, Ruth

2014-12-01

Purpose: To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. Methods and Materials: A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared betweenmore » patients with and without HSVs. Results: The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm{sup 3}) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm{sup 3} vs 63.4 cm{sup 3}; P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs. Conclusions: Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted.« 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

Proton-proton correlations observed in two-proton radioactivity of 94Ag.

PubMed

Mukha, Ivan; Roeckl, Ernst; Batist, Leonid; Blazhev, Andrey; Döring, Joachim; Grawe, Hubert; Grigorenko, Leonid; Huyse, Mark; Janas, Zenon; Kirchner, Reinhard; La Commara, Marco; Mazzocchi, Chiara; Tabor, Sam L; Van Duppen, Piet

2006-01-19

The stability and spontaneous decay of naturally occurring atomic nuclei have been much studied ever since Becquerel discovered natural radioactivity in 1896. In 1960, proton-rich nuclei with an odd or an even atomic number Z were predicted to decay through one- and two-proton radioactivity, respectively. The experimental observation of one-proton radioactivity was first reported in 1982, and two-proton radioactivity has now also been detected by experimentally studying the decay properties of 45Fe (refs 3, 4) and 54Zn (ref. 5). Here we report proton-proton correlations observed during the radioactive decay of a spinning long-lived state of the lightest known isotope of silver, 94Ag, which is known to undergo one-proton decay. We infer from these correlations that the long-lived state must also decay through simultaneous two-proton emission, making 94Ag the first nucleus to exhibit one- as well as two-proton radioactivity. We attribute the two-proton emission behaviour and the unexpectedly large probability for this decay mechanism to a very large deformation of the parent nucleus into a prolate (cigar-like) shape, which facilitates emission of protons either from the same or from opposite ends of the 'cigar'.

Effects of hydrogen bonding on amide-proton chemical shift anisotropy in a proline-containing model peptide

NASA Astrophysics Data System (ADS)

Pichumani, Kumar; George, Gijo; Hebbar, Sankeerth; Chatterjee, Bhaswati; Raghothama, Srinivasarao

2015-05-01

Longitudinal relaxation due to cross-correlation between dipolar (1HN-1Hα) and amide-proton chemical shift anisotropy (1HN CSA) has been measured in a model tripeptide Piv-LPro-LPro-LPhe-OMe. The peptide bond across diproline segment is known to undergo cis/trans isomerization and only in the cis form does the lone Phe amide-proton become involved in intramolecular hydrogen bonding. The strength of the cross correlated relaxation interference is found to be significantly different between cis and trans forms, and this difference is shown as an influence of intramolecular hydrogen bonding on the amide-proton CSA.

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.

Dosimetric advantages of IMPT over IMRT for laser-accelerated proton beams

NASA Astrophysics Data System (ADS)

Luo, W.; Li, J.; Fourkal, E.; Fan, J.; Xu, X.; Chen, Z.; Jin, L.; Price, R.; Ma, C.-M.

2008-12-01

As a clinical application of an exciting scientific breakthrough, a compact and cost-efficient proton therapy unit using high-power laser acceleration is being developed at Fox Chase Cancer Center. The significance of this application depends on whether or not it can yield dosimetric superiority over intensity-modulated radiation therapy (IMRT). The goal of this study is to show how laser-accelerated proton beams with broad energy spreads can be optimally used for proton therapy including intensity-modulated proton therapy (IMPT) and achieve dosimetric superiority over IMRT for prostate cancer. Desired energies and spreads with a varying δE/E were selected with the particle selection device and used to generate spread-out Bragg peaks (SOBPs). Proton plans were generated on an in-house Monte Carlo-based inverse-planning system. Fifteen prostate IMRT plans previously used for patient treatment have been included for comparison. Identical dose prescriptions, beam arrangement and consistent dose constrains were used for IMRT and IMPT plans to show the dosimetric differences that were caused only by the different physical characteristics of proton and photon beams. Different optimization constrains and beam arrangements were also used to find optimal IMPT. The results show that conventional proton therapy (CPT) plans without intensity modulation were not superior to IMRT, but IMPT can generate better proton plans if appropriate beam setup and optimization are used. Compared to IMRT, IMPT can reduce the target dose heterogeneity ((D5-D95)/D95) by up to 56%. The volume receiving 65 Gy and higher (V65) for the bladder and the rectum can be reduced by up to 45% and 88%, respectively, while the volume receiving 40 Gy and higher (V40) for the bladder and the rectum can be reduced by up to 49% and 68%, respectively. IMPT can also reduce the whole body non-target tissue dose by up to 61% or a factor 2.5. This study has shown that the laser accelerator under development has a potential to generate high-quality proton beams for cancer treatment. Significant improvement in target dose uniformity and normal tissue sparing as well as in reduction of whole body dose can be achieved by IMPT with appropriate optimization and beam setup.

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

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

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.

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.

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

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

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

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).

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

Animal-Assisted Therapy for Patients Undergoing Treatment at NIH Clinical Center | NIH MedlinePlus the Magazine

MedlinePlus

... this page please turn JavaScript on. Feature: Therapy Dogs Animal-Assisted Therapy for Patients Undergoing Treatment at ... Kerry (middle), a patient, is with the therapy dog team of Jeanette Golden (left) and Tucker the ...

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

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.

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

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.

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.

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

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

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.

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

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.

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

Carlson, D.

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

Anhydrous Proton-Conducting Membranes for Fuel Cells

NASA Technical Reports Server (NTRS)

Narayanan, Sekharipuram; Yen, Shiao-Pin S.

2005-01-01

Polymeric electrolyte membranes that do not depend on water for conduction of protons are undergoing development for use in fuel cells. Prior polymeric electrolyte fuel-cell membranes (e.g., those that contain perfluorosulfonic acid) depend on water and must be limited to operation below a temperature of 125 C because they retain water poorly at higher temperatures. In contrast, the present developmental anhydrous membranes are expected to function well at temperatures up to 200 C. The developmental membranes exploit a hopping-and-reorganization proton- conduction process that can occur in the solid state in organic amine salts and is similar to a proton-conduction process in a liquid. This process was studied during the 1970s, but until now, there has been no report of exploiting organic amine salts for proton conduction in fuel cells.

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.

Using Gas-Phase Guest-Host Chemistry to Probe the Structures of b Ions of Peptides

NASA Astrophysics Data System (ADS)

Somogyi, Árpád; Harrison, Alex G.; Paizs, Béla

2012-12-01

Middle-sized b n ( n ≥ 5) fragments of protonated peptides undergo selective complex formation with ammonia under experimental conditions typically used to probe hydrogen-deuterium exchange in Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Other usual peptide fragments like y, a, a*, etc., and small b n ( n ≤ 4) fragments do not form stable ammonia adducts. We propose that complex formation of b n ions with ammonia is characteristic to macrocyclic isomers of these fragments. Experiments on a protonated cyclic peptide and N-terminal acetylated peptides fully support this hypothesis; the protonated cyclic peptide does form ammonia adducts while linear b n ions of acetylated peptides do not undergo complexation. Density functional theory (DFT) calculations on the proton-bound dimers of all-Ala b 4 , b 5 , and b 7 ions and ammonia indicate that the ionizing proton initially located on the peptide fragment transfers to ammonia upon adduct formation. The ammonium ion is then solvated by N+-H…O H-bonds; this stabilization is much stronger for macrocyclic b n isomers due to the stable cage-like structure formed and entropy effects. The present study demonstrates that gas-phase guest-host chemistry can be used to selectively probe structural features (i.e., macrocyclic or linear) of fragments of protonated peptides. Stable ammonia adducts of b 9 , b 9 -A, and b 9 -2A of A8YA, and b 13 of A20YVFL are observed indicating that even these large b-type ions form macrocyclic structures.

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.

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.

Clinical Practice Update: The Use of Per-Oral Endoscopic Myotomy in Achalasia: Expert Review and Best Practice Advice From the AGA Institute.

PubMed

Kahrilas, Peter J; Katzka, David; Richter, Joel E

2017-11-01

The purpose of this review is to describe a place for per-oral endoscopic myotomy (POEM) among the currently available robust treatments for achalasia. The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed and EMbase. The Clinical Practice Updates Committee of the American Gastroenterological Association proposes the following recommendations: 1) in determining the need for achalasia therapy, patient-specific parameters (Chicago Classification subtype, comorbidities, early vs late disease, primary or secondary causes) should be considered along with published efficacy data; 2) given the complexity of this procedure, POEM should be performed by experienced physicians in high-volume centers because an estimated 20-40 procedures are needed to achieve competence; 3) if the expertise is available, POEM should be considered as primary therapy for type III achalasia; 4) if the expertise is available, POEM should be considered as treatment option comparable with laparoscopic Heller myotomy for any of the achalasia syndromes; and 5) post-POEM patients should be considered high risk to develop reflux esophagitis and advised of the management considerations (potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy) of this before undergoing the procedure. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

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.

[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.

An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy.

PubMed

Hirayama, Shusuke; Matsuura, Taeko; Ueda, Hideaki; Fujii, Yusuke; Fujii, Takaaki; Takao, Seishin; Miyamoto, Naoki; Shimizu, Shinichi; Fujimoto, Rintaro; Umegaki, Kikuo; Shirato, Hiroki

2018-05-22

To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LET d ) is required. In this study, we have developed the analytical LET d calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LET d value for the lateral distribution of a pencil beam, the actual LET d increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LET d behavior, we have assumed that the LETs of primary and halo components can take different values (LET p and LET halo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LET d distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LET d distributions and mean LET d (LET d,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. In the homogeneous phantom, the LET d profiles obtained by the dual-LET kernels agree well with the MCS results except for the low-dose region in the lateral penumbra, where the actual dose was below 10% of the maximum dose. In the patient geometry, the LET d profiles calculated with the developed method reproduces MCS with the similar accuracy as in the homogeneous phantom. The maximum differences in LET d,mean for each structure between the PBA-dLET and the MCS were 0.06 keV/μm in homogeneous phantoms and 0.08 keV/μm in patient geometries under all tested conditions, respectively. We confirmed that the dual-LET-kernel model well reproduced the MCS, not only in the homogeneous phantom but also in complex patient geometries. The accuracy of the LET d was largely improved from the single-LET-kernel model, especially at the lateral penumbra. The model is expected to be useful, especially for proper recognition of the risk of side effects when the target is next to critical organs. © 2018 American Association of Physicists in Medicine.

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.

Hydrolysis of N3-methyl-2'-deoxycytidine: model compound for reactivity of protonated cytosine residues in DNA.

PubMed

Sowers, L C; Sedwick, W D; Shaw, B R

1989-11-01

Protonation of cytosine residues at physiological pH may occur in DNA as a consequence of both alkylation and aberrant base-pair formation. When cytosine derivatives are protonated, they undergo hydrolysis reactions at elevated rates and can either deaminate to form the corresponding uracil derivatives or depyrimidinate generating abasic sites. The kinetic parameters for reaction of protonated cytosine are derived by studying the hydrolysis of N3-methyl-2'-deoxycytidine (m3dC), a cytosine analogue which is predominantly protonated at physiological pH. Both deamination and depyrimidimation reaction rates are shown to be linearly dependent upon the fraction of protonated molecules. We present here thermodynamic parameters which allow determination of hydrolysis rates of m3dC as functions of pH and temperature. Protonation of cytosine residues in DNA, as induced by aberrant base-pair formation or base modification, may accelerate the rate of both deamination and depyrimidation up to several thousand-fold under physiological conditions.

Aqueous proton transfer across single-layer graphene

DOE PAGES

Achtyl, Jennifer L.; Unocic, Raymond R.; Xu, Lijun; ...

2015-03-17

Proton transfer across single-layer graphene proceeds with large computed energy barriers and is thought to be unfavourable at room temperature unless nanoscale holes or dopants are introduced, or a potential bias is applied. Here we subject single-layer graphene supported on fused ​silica to cycles of high and low pH, and show that protons transfer reversibly from the aqueous phase through the graphene to the other side where they undergo acid–base chemistry with the silica hydroxyl groups. After ruling out diffusion through macroscopic pinholes, the protons are found to transfer through rare, naturally occurring atomic defects. Computer simulations reveal low energymore » barriers of 0.61–0.75 eV for aqueous proton transfer across hydroxyl-terminated atomic defects that participate in a Grotthuss-type relay, while ​pyrylium-like ether terminations shut down proton exchange. In conclusion, unfavourable energy barriers to helium and ​hydrogen transfer indicate the process is selective for aqueous protons.« less

Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven ⁹Be(p, n) boron neutron capture therapy neutron source.

PubMed

Hashimoto, Y; Hiraga, F; Kiyanagi, Y

2015-12-01

We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Video Material as an Effective Educational Tool to Address Informational and Educational Needs of Cancer Patients Undergoing Radiation Therapy.

PubMed

Nathoo, Dilshad

2017-06-01

With increasing rates of cancer patients undergoing radiation therapy, the treatment itself can cause patients significant amounts of anxiety and distress. This can be attributed to the diagnosis of the disease, lack of knowledge of what radiation therapy is, expectations and management of side effects, and the lack of knowledge of supportive care for patients and their families. Providing patients with effective educational tools to meet the informational needs of cancer patients undergoing radiation therapy can empower patients and allow them to participate in treatment decision-making and their own healthcare. This discussion paper will evaluate several studies on the psychological impact of cancer patients undergoing radiation therapy and how video material can effectively meet the informational and educational needs of this patient population group.

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.

Protonation switching to the least-basic heteroatom of carbamate through cationic hydrogen bonding promotes the formation of isocyanate cations.

PubMed

Kurouchi, Hiroaki; Sumita, Akinari; Otani, Yuko; Ohwada, Tomohiko

2014-07-07

We found that phenethylcarbamates that bear ortho-salicylate as an ether group (carbamoyl salicylates) dramatically accelerate OC bond dissociation in strong acid to facilitate generation of isocyanate cation (N-protonated isocyanates), which undergo subsequent intramolecular aromatic electrophilic cyclization to give dihydroisoquinolones. To generate isocyanate cations from carbamates in acidic media as electrophiles for aromatic substitution, protonation at the ether oxygen, the least basic heteroatom, is essential to promote CO bond cleavage. However, the carbonyl oxygen of carbamates, the most basic site, is protonated exclusively in strong acids. We found that the protonation site can be shifted to an alternative basic atom by linking methyl salicylate to the ether oxygen of carbamate. The methyl ester oxygen ortho to the phenolic (ether) oxygen of salicylate is as basic as the carbamate carbonyl oxygen, and we found that monoprotonation at the methyl ester oxygen in strong acid resulted in the formation of an intramolecular cationic hydrogen bond (>CO(+) H⋅⋅⋅O<) with the phenolic ether oxygen. This facilitates OC bond dissociation of phenethylcarbamates, thereby promoting isocyanate cation formation. In contrast, superacid-mediated diprotonation at the methyl ester oxygen of the salicylate and the carbonyl oxygen of the carbamate afforded a rather stable dication, which did not readily undergo CO bond dissociation. This is an unprecedented and unknown case in which the monocation has greater reactivity than the dication. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol.

PubMed

Bennett, Marsha; Bonanno, Laura; Kuhn, William

2016-10-01

The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?

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

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

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

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

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

SU-E-T-182: Feasibility of Dose Painting by Numbers in Proton Therapy with Contour-Driven Plan Optimization

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

Montero, A Barragan; Differding, S; Lee, J

Purpose: The work aims to 1) prove the feasibility of dose painting by numbers (DPBN) in proton therapy with usual contour-driven plan optimization and 2) compare the achieved plan quality to that of rotational IMRT. Methods: For two patients with head and neck cancers, voxel-by-voxel prescription to the target volume (PTV-PET) was calculated from {sup 18} FDG-PET images and converted to contour-based prescription by defining several sub-contours. Treatments were planned with RayStation (RaySearch Laboratories, Sweden) and proton pencil beam scanning modality. In order to determine the optimal plan parameters to approach the DPBN prescription, the effect of the number ofmore » fields, number of sub-contours and use of range shifter were tested separately on each patient. The number of sub-contours were increased from 3 to 11 while the number of fields were set to 3, 5, 7 and 9. Treatment plans were also optimized on two rotational IMRT systems (TomoTherapy and Varian RapidArc) using previously published guidelines. Results: For both patients, more than 99% of the PTV-PET received at least 95% of the prescribed dose while less than 1% of the PTV-PET received more than 105%, which demonstrates the feasibility of the treatment. Neither the use of a range shifter nor the increase of the number of fields had a significant influence on PTV coverage. Plan quality increased when increasing number of fields up to 7 or 9 and slightly decreased for a bigger number of sub-contours. Good OAR sparing is achieved while keeping high plan quality. Finally, proton therapy achieved significantly better plan quality than rotational IMRT. Conclusion: Voxel-by-voxel prescriptions can be approximated accurately in proton therapy using a contour-driven optimization. Target coverage is nearly insensitive to the number of fields and the use of a range shifter. Finally, plan quality assessment confirmed the superiority of proton therapy compared to rotational IMRT.« less

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

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.

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.

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-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

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

Taleei, R; Qin, N; Jiang, S

2016-06-15

Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relativemore » Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.« less

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. ...

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.

Magnetic resonance safety and compatibility of tantalum markers used in proton beam therapy for intraocular tumors: A 7.0 Tesla study.

PubMed

Oberacker, Eva; Paul, Katharina; Huelnhagen, Till; Oezerdem, Celal; Winter, Lukas; Pohlmann, Andreas; Boehmert, Laura; Stachs, Oliver; Heufelder, Jens; Weber, Andreas; Rehak, Matus; Seibel, Ira; Niendorf, Thoralf

2017-10-01

Proton radiation therapy (PRT) is a standard treatment of uveal melanoma. PRT patients undergo implantation of ocular tantalum markers (OTMs) for treatment planning. Ultra-high-field MRI is a promising technique for 3D tumor visualization and PRT planning. This work examines MR safety and compatibility of OTMs at 7.0 Tesla. MR safety assessment included deflection angle measurements (DAMs), electromagnetic field (EMF) simulations for specific absorption rate (SAR) estimation, and temperature simulations for examining radiofrequency heating using a bow-tie dipole antenna for transmission. MR compatibility was assessed by susceptibility artifacts in agarose, ex vivo pig eyes, and in an ex vivo tumor eye using gradient echo and fast spin-echo imaging. DAM (α < 1 °) demonstrated no risk attributed to magnetically induced OTM deflection. EMF simulations showed that an OTM can be approximated by a disk, demonstrated the need for averaging masses of m ave  = 0.01 g to accommodate the OTM, and provided SAR 0.01g,maximum  = 2.64 W/kg (P in  = 1W) in OTM presence. A transfer function was derived, enabling SAR 0.01g estimation for individual patient scenarios without the OTM being integrated. Thermal simulations revealed minor OTM-related temperature increase (δT < 15 mK). Susceptibility artifact size (<8 mm) and location suggest no restrictions for MRI of the nervus opticus. OTMs are not a per se contraindication for MRI. Magn Reson Med 78:1533-1546, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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

Characterization of the microbunch time structure of proton pencil beams at a clinical treatment facility.

PubMed

Petzoldt, J; Roemer, K E; Enghardt, W; Fiedler, F; Golnik, C; Hueso-González, F; Helmbrecht, S; Kormoll, T; Rohling, H; Smeets, J; Werner, T; Pausch, G

2016-03-21

Proton therapy is an advantageous treatment modality compared to conventional radiotherapy. In contrast to photons, charged particles have a finite range and can thus spare organs at risk. Additionally, the increased ionization density in the so-called Bragg peak close to the particle range can be utilized for maximum dose deposition in the tumour volume. Unfortunately, the accuracy of the therapy can be affected by range uncertainties, which have to be covered by additional safety margins around the treatment volume. A real-time range and dose verification is therefore highly desired and would be key to exploit the major advantages of proton therapy. Prompt gamma rays, produced in nuclear reactions between projectile and target nuclei, can be used to measure the proton's range. The prompt gamma-ray timing (PGT) method aims at obtaining this information by determining the gamma-ray emission time along the proton path using a conventional time-of-flight detector setup. First tests at a clinical accelerator have shown the feasibility to observe range shifts of about 5 mm at clinically relevant doses. However, PGT spectra are smeared out by the bunch time spread. Additionally, accelerator related proton bunch drifts against the radio frequency have been detected, preventing a potential range verification. At OncoRay, first experiments using a proton bunch monitor (PBM) at a clinical pencil beam have been conducted. Elastic proton scattering at a hydrogen-containing foil could be utilized to create a coincident proton-proton signal in two identical PBMs. The selection of coincident events helped to suppress uncorrelated background. The PBM setup was used as time reference for a PGT detector to correct for potential bunch drifts. Furthermore, the corrected PGT data were used to image an inhomogeneous phantom. In a further systematic measurement campaign, the bunch time spread and the proton transmission rate were measured for several beam energies between 69 and 225 MeV as well as for variable momentum limiting slit openings. We conclude that the usage of a PBM increases the robustness of the PGT method in clinical conditions and that the obtained data will help to create reliable range verification procedures in clinical routine.

Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

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

Pugh, Thomas J.; Munsell, Mark F.; Choi, Seungtaek

Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence ofmore » modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient cohort are warranted.« less

Outcomes of proton therapy for the treatment of uveal metastases.

PubMed

Kamran, Sophia C; Collier, John M; Lane, Anne Marie; Kim, Ivana; Niemierko, Andrzej; Chen, Yen-Lin E; MacDonald, Shannon M; Munzenrider, John E; Gragoudas, Evangelos; Shih, Helen A

2014-12-01

Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year. Copyright © 2014 Elsevier Inc. All rights reserved.

Outcomes of Proton Therapy for the Treatment of Uveal Metastases

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

Kamran, Sophia C.; Collier, John M.; Lane, Anne Marie

2014-12-01

Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patientsmore » were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year.« less

Design, construction and tests of a 3 GHz proton linac booster (LIBO) for cancer therapy

NASA Astrophysics Data System (ADS)

Berra, Paolo

2007-12-01

In the last ten years the use of proton beams in radiation therapy has become a clinical tool for treatment of deep-seated tumours. LIBO is a RF compact and low cost proton linear accelerator (SCL type) for hadrontherapy. It is conceived by TERA Foundation as a 3 GHz Linac Booster, to be mounted downstream of an existing cyclotron in order to boost the energy of the proton beam up to 200 MeV, needed for deep treatment (~25 cm) in the human body. With this solution it is possible to transform a low energy commercial cyclotron, normally used for eye melanoma therapy, isotope production and nuclear physics research, into an accelerator for deep-seated tumours. A prototype module of LIBO has been built and successfully tested with full RF power at CERN and with proton beam at INFN Laboratori Nazionali del Sud (LNS) in Catania, within an international collaboration between TERA Foundation, CERN, the Universities and INFN groups of Milan and Naples. The mid-term aim of the project is the technology transfer of the accumulated know-how to a consortium of companies and to bring this novel medical tool to hospitals. The design, construction and tests of the LIBO prototype are described in detail.

Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications.

PubMed

Wolff, Hendrik Andreas; Wagner, Daniela Melanie; Conradi, Lena-Christin; Hennies, Steffen; Ghadimi, Michael; Hess, Clemens Friedrich; Christiansen, Hans

2012-01-01

Ongoing clinical trials aim to improve local control and overall survival rates by intensification of therapy regimen for patients with locally advanced rectal cancer. It is well known that whenever treatment is intensified, risk of therapy-related toxicity rises. An irradiation with protons could possibly present an approach to solve this dilemma by lowering the exposure to the organs-at-risk (OAR) without compromising tumor response. Twenty five consecutive patients were treated from 04/2009 to 5/2010. For all patients, four different treatment plans including protons, RapidArc, IMRT and 3D-conformal-technique were retrospectively calculated and analyzed according to dosimetric aspects. Detailed DVH-analyses revealed that protons clearly reduced the dose to the OAR and entire normal tissue when compared to other techniques. Furthermore, the conformity index was significantly better and target volumes were covered consistent with the ICRU guidelines. Planning results suggest that treatment with protons can improve the therapeutic tolerance for the irradiation of rectal cancer, particularly for patients scheduled for an irradiation with an intensified chemotherapy regimen and identified to be at high risk for acute therapy-related toxicity. However, clinical experiences and long-term observation are needed to assess tumor response and related toxicity rates. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Two-dimensional dosimetry of radiotherapeutical proton beams using thermoluminescence foils.

PubMed

Czopyk, L; Klosowski, M; Olko, P; Swakon, J; Waligorski, M P R; Kajdrowicz, T; Cuttone, G; Cirrone, G A P; Di Rosa, F

2007-01-01

In modern radiation therapy such as intensity modulated radiation therapy or proton therapy, one is able to cover the target volume with improved dose conformation and to spare surrounding tissue with help of modern measurement techniques. Novel thermoluminescence dosimetry (TLD) foils, developed from the hot-pressed mixture of LiF:Mg,Cu,P (MCP TL) powder and ethylene-tetrafluoroethylene (ETFE) copolymer, have been applied for 2-D dosimetry of radiotherapeutical proton beams at INFN Catania and IFJ Krakow. A TLD reader with 70 mm heating plate and CCD camera was used to read the 2-D emission pattern of irradiated foils. The absorbed dose profiles were evaluated, taking into account correction factors specific for TLD such as dose and energy response. TLD foils were applied for measuring of dose distributions within an eye phantom and compared with predictions obtained from the MCNPX code and Eclipse Ocular Proton Planning (Varian Medical Systems) clinical radiotherapy planning system. We demonstrate the possibility of measuring 2-D dose distributions with point resolution of about 0.5 x 0.5 mm(2).

SU-F-T-174: Patient-Specific Point Dose Measurement Using Fiber Optic Radiation Sensor Using Cerenkov Radiation for Proton Therapeutic Beam

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

Son, J; National Cancer Center, Goyang-si; Kim, M

Purpose: A fiber-optic radiation sensor using Cerenkov radiation (FOCR) has been widely studied for use as a dosimeter for proton therapeutic beam. We developed the FOCR, and it applied to patient-specific point dose measurement in order to evaluate the effectiveness of the FOCR system for proton therapy QA. Methods: Calibration of FOCR was performed with an ionization chamber whose absolute doses were determined according to the IAEA TRS-398 protocol. To determine the calibration curve, the FOCR was irradiated perpendicularly to the proton beam at the 13 dose levels steps. We selected five actual patient treatment plans performed at proton therapymore » center and compared the resulting FOCR measurements with the ionization chamber measurements. Results: The Cerenkov light yield of the FOCR increases linearly with as the dose measured using the ionization chamber increases from 0 cGy to 500 cGy. The results indicate that the fitting curve is linear, suggesting that dose measurement based on the light yield of the FOCR is possible. The results of proton radiation dose QA performed using the FOCR for 10 proton fields and five patients are good agreement with an ionization chamber. Conclusion: We carried out the patient QA using the FOCR for proton therapeutic beam and evaluated the effectiveness of the FOCR as a proton therapy QA tool. Our results indicate that the FOCR is suitable for use in patient QA of clinical proton beams.« less

SU-E-T-482: In Vivo Dosimetry of An Anthropomorphic Phantom by Using the RADPOS System for Proton Beam Therapy

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

Kohno, R; Motegi, K; Hotta, K

Purpose: Delivered doses in an anthropomorphic phantom were evaluated by using the RADPOS system for proton beam therapy. Methods: The RADPOS in vivo dosimetry system combines an electromagnetic positioning sensor with MOSFET dosimetry, allowing simultaneous online measurements of dose and spatial position. Through the RADPOS system, dose evaluation points can be determined. In vivo proton dosimetry was evaluated by using the RADPOS system and anthropomorphic head and neck phantom. MOSFET doses measured at 3D positions obtained with the RADPOS were compared to the treatment plan values that were calculated by a simplified Monte Carlo (SMC) method. Although the MOSFET responsemore » depends strongly on the linear energy transfer (LET) of proton beam, the MOSFET responses to proton beams were corrected with the SMC. Here, the SMC calculated only dose deposition determined by the experimental depth–dose distribution and lateral displacement of protons due to both multiple scattering effect in materials and incident angle. As a Result, the SMC could quickly calculate accurate doses in even heterogeneities. Results: In vivo dosimetry by using the RADPOS, as well as the MOSFET doses agreed in comparison with calculations by the SMC in the range of −3.0% to 8.3%. Most measurement errors occurred because of the uncertainties of dose calculations due to the position error of 1 mm. Conclusion: We evaluated the delivered doses in the anthropomorphic phantom by using the RADPOS system for proton beam therapy. The MOSFET doses agreed in comparison with calculations by the SMC within the measurement error. Therefore, we could successfully control the uncertainties of the measurement positions by using the RADPOS system within 1 mm in in vivo proton dosimetry. We aim for the clinical application of in vivo proton dosimetry with this RADPOS system.« less

Neutrons in proton pencil beam scanning: parameterization of energy, quality factors and RBE

NASA Astrophysics Data System (ADS)

Schneider, Uwe; Hälg, Roger A.; Baiocco, Giorgio; Lomax, Tony

2016-08-01

The biological effectiveness of neutrons produced during proton therapy in inducing cancer is unknown, but potentially large. In particular, since neutron biological effectiveness is energy dependent, it is necessary to estimate, besides the dose, also the energy spectra, in order to obtain quantities which could be a measure of the biological effectiveness and test current models and new approaches against epidemiological studies on cancer induction after proton therapy. For patients treated with proton pencil beam scanning, this work aims to predict the spatially localized neutron energies, the effective quality factor, the weighting factor according to ICRP, and two RBE values, the first obtained from the saturation corrected dose mean lineal energy and the second from DSB cluster induction. A proton pencil beam was Monte Carlo simulated using GEANT. Based on the simulated neutron spectra for three different proton beam energies a parameterization of energy, quality factors and RBE was calculated. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed parameterizations in order to calculate the spatially localized neutron energy, quality factors and RBE for each treated patient. The parameterization represents the simple quantification of neutron energy in two energy bins and the quality factors and RBE with a satisfying precision up to 85 cm away from the proton pencil beam when compared to the results based on 3D Monte Carlo simulations. The root mean square error of the energy estimate between Monte Carlo simulation based results and the parameterization is 3.9%. For the quality factors and RBE estimates it is smaller than 0.9%. The model was successfully integrated into the PSI treatment planning system. It was found that the parameterizations for neutron energy, quality factors and RBE were independent of proton energy in the investigated energy range of interest for proton therapy. The pencil beam algorithm has been extended using the developed parameterizations in order to calculate the neutron energy, quality factor and RBE.

Neutrons in proton pencil beam scanning: parameterization of energy, quality factors and RBE.

PubMed

Schneider, Uwe; Hälg, Roger A; Baiocco, Giorgio; Lomax, Tony

2016-08-21

The biological effectiveness of neutrons produced during proton therapy in inducing cancer is unknown, but potentially large. In particular, since neutron biological effectiveness is energy dependent, it is necessary to estimate, besides the dose, also the energy spectra, in order to obtain quantities which could be a measure of the biological effectiveness and test current models and new approaches against epidemiological studies on cancer induction after proton therapy. For patients treated with proton pencil beam scanning, this work aims to predict the spatially localized neutron energies, the effective quality factor, the weighting factor according to ICRP, and two RBE values, the first obtained from the saturation corrected dose mean lineal energy and the second from DSB cluster induction. A proton pencil beam was Monte Carlo simulated using GEANT. Based on the simulated neutron spectra for three different proton beam energies a parameterization of energy, quality factors and RBE was calculated. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed parameterizations in order to calculate the spatially localized neutron energy, quality factors and RBE for each treated patient. The parameterization represents the simple quantification of neutron energy in two energy bins and the quality factors and RBE with a satisfying precision up to 85 cm away from the proton pencil beam when compared to the results based on 3D Monte Carlo simulations. The root mean square error of the energy estimate between Monte Carlo simulation based results and the parameterization is 3.9%. For the quality factors and RBE estimates it is smaller than 0.9%. The model was successfully integrated into the PSI treatment planning system. It was found that the parameterizations for neutron energy, quality factors and RBE were independent of proton energy in the investigated energy range of interest for proton therapy. The pencil beam algorithm has been extended using the developed parameterizations in order to calculate the neutron energy, quality factor and RBE.

TU-G-BRB-04: Digital Phantoms for Developing Protocols in Particle Therapy

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

Lee, C.

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-02: Clinical Trials in Particle Therapy - Open Questions

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

Choy, H.

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

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

Supanich, M.

The International Electrotechnical Commission (IEC) writes standards that manufacturers of electrical equipment must comply with. Medical electrical equipment, such as medical imaging, radiation therapy, and radiation dosimetry devices, fall under Technical Committee 62. Of particular interest to medical physicists are the standards developed within Subcommittees (SC) 62B, which addresses diagnostic radiological imaging equipment, and 62C, which addresses equipment for radiation therapy, nuclear medicine and dosimetry. For example, a Working Group of SC 62B is responsible for safety and quality assurance standards for CT scanners and a Working Group of SC 62C is responsible for standards that set requirements for dosimetricmore » safety and accuracy of linacs and proton accelerators. IEC standards thus have an impact on every aspect of a medical physicist’s job, including equipment testing, shielding design, room layout, and workflow. Consequently, it is imperative that US medical physicists know about existing standards, as well as have input on those under development or undergoing revision. The structure of the IEC and current standards development work will be described in detail. The presentation will explain how US medical physicists can learn about IEC standards and contribute to their development. Learning Objectives: Learn about the structure of the IEC and the influence that IEC standards have on the design of equipment for radiology and radiation therapy. Learn about the mechanisms by which the US participates in the development and revision of standards. Understand the specific requirements of several standards having direct relevance to diagnostic and radiation therapy physicists.« less

Protonation and Proton-Coupled Electron Transfer at S-Ligated [4Fe-4S] Clusters

PubMed Central

Morris, Wesley D.; Darcy, Julia W.; Mayer, James M.

2015-01-01

Biological [Fe-S] clusters are increasingly recognized to undergo proton-coupled electron transfer (PCET), but the site of protonation, mechanism, and role for PCET remains largely unknown. Here we explore this reactivity with synthetic model clusters. Protonation of the arylthiolate-ligated [4Fe-4S] cluster [Fe4S4(SAr)4]2- (1, SAr = S-2,4-6-(iPr)3C6H2) leads to thiol dissociation, reversibly forming [Fe4S4(SAr)3L]1- (2) + ArSH (L = solvent, and/or conjugate base). Solutions of 2 + ArSH react with the nitroxyl radical TEMPO to give [Fe4S4(SAr)4]1- (1ox) and TEMPOH. This reaction involves PCET coupled to thiolate association and may proceed via the unobserved protonated cluster [Fe4S4(SAr)3(HSAr)]1-(1-H). Similar reactions with this and related clusters proceed comparably. An understanding of the PCET thermochemistry of this cluster system has been developed, encompassing three different redox levels and two protonation states. PMID:25965413

Unraveling the mechanism of proton translocation in the extracellular half-channel of bacteriorhodopsin.

PubMed

Ge, Xiaoxia; Gunner, M R

2016-05-01

Bacteriorhodopsin, a light activated protein that creates a proton gradient in halobacteria, has long served as a simple model of proton pumps. Within bacteriorhodopsin, several key sites undergo protonation changes during the photocycle, moving protons from the higher pH cytoplasm to the lower pH extracellular side. The mechanism underlying the long-range proton translocation between the central (the retinal Schiff base SB216, D85, and D212) and exit clusters (E194 and E204) remains elusive. To obtain a dynamic view of the key factors controlling proton translocation, a systematic study using molecular dynamics simulation was performed for eight bacteriorhodopsin models varying in retinal isomer and protonation states of the SB216, D85, D212, and E204. The side-chain orientation of R82 is determined primarily by the protonation states of the residues in the EC. The side-chain reorientation of R82 modulates the hydrogen-bond network and consequently possible pathways of proton transfer. Quantum mechanical intrinsic reaction coordinate calculations of proton-transfer in the methyl guanidinium-hydronium-hydroxide model system show that proton transfer via a guanidinium group requires an initial geometry permitting proton donation and acceptance by the same amine. In all the bacteriorhodopsin models, R82 can form proton wires with both the CC and the EC connected by the same amine. Alternatively, rare proton wires for proton transfer from the CC to the EC without involving R82 were found in an O' state where the proton on D85 is transferred to D212. © 2016 Wiley Periodicals, Inc.

Beam-on imaging of short-lived positron emitters during proton therapy

NASA Astrophysics Data System (ADS)

Buitenhuis, H. J. T.; Diblen, F.; Brzezinski, K. W.; Brandenburg, S.; Dendooven, P.

2017-06-01

In vivo dose delivery verification in proton therapy can be performed by positron emission tomography (PET) of the positron-emitting nuclei produced by the proton beam in the patient. A PET scanner installed in the treatment position of a proton therapy facility that takes data with the beam on will see very short-lived nuclides as well as longer-lived nuclides. The most important short-lived nuclide for proton therapy is 12N (Dendooven et al 2015 Phys. Med. Biol. 60 8923-47), which has a half-life of 11 ms. The results of a proof-of-principle experiment of beam-on PET imaging of short-lived 12N nuclei are presented. The Philips Digital Photon Counting Module TEK PET system was used, which is based on LYSO scintillators mounted on digital SiPM photosensors. A 90 MeV proton beam from the cyclotron at KVI-CART was used to investigate the energy and time spectra of PET coincidences during beam-on. Events coinciding with proton bunches, such as prompt gamma rays, were removed from the data via an anti-coincidence filter with the cyclotron RF. The resulting energy spectrum allowed good identification of the 511 keV PET counts during beam-on. A method was developed to subtract the long-lived background from the 12N image by introducing a beam-off period into the cyclotron beam time structure. We measured 2D images and 1D profiles of the 12N distribution. A range shift of 5 mm was measured as 6  ±  3 mm using the 12N profile. A larger, more efficient, PET system with a higher data throughput capability will allow beam-on 12N PET imaging of single spots in the distal layer of an irradiation with an increased signal-to-background ratio and thus better accuracy. A simulation shows that a large dual panel scanner, which images a single spot directly after it is delivered, can measure a 5 mm range shift with millimeter accuracy: 5.5  ±  1.1 mm for 1  ×  108 protons and 5.2  ±  0.5 mm for 5  ×  108 protons. This makes fast and accurate feedback on the dose delivery during treatment possible.

Application of nuclear physics in medical physics and nuclear medicine

NASA Astrophysics Data System (ADS)

Hoehr, Cornelia

2016-09-01

Nuclear physics has a long history of influencing and advancing medical fields. At TRIUMF we use the applications of nuclear physics to diagnose several diseases via medical isotopes and treat cancer by using proton beams. The Life Science division has a long history of producing Positron Emission Tomography (PET) isotopes but we are also investigating the production of SPECT and PET isotopes with a potential shortage for clinical operation or otherwise limited access to chemists, biologists and medical researchers. New targets are being developed, aided by a simulation platform investigating the processes inside a target under proton irradiation - nuclear, thermodynamic, and chemical. Simulations also aid in the development of new beam-shaping devices for TRIUMF's Proton Therapy facility, Canada's only proton therapy facility, as well as new treatment testing systems. Both promise improved treatment delivery for cancer patients.

Fractionated Proton Radiotherapy for Benign Cavernous Sinus Meningiomas

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

Slater, Jerry D., E-mail: jdslater@dominion.llumc.edu; Loredo, Lilia N.; Chung, Arthur

2012-08-01

Purpose: To evaluate the efficacy of fractionated proton radiotherapy for a population of patients with benign cavernous sinus meningiomas. Methods and Materials: Between 1991 and 2002, 72 patients were treated at Loma Linda University Medical Center with proton therapy for cavernous sinus meningiomas. Fifty-one patients had biopsy or subtotal resection; 47 had World Health Organization grade 1 pathology. Twenty-one patients had no histologic verification. Twenty-two patients received primary proton therapy; 30 had 1 previous surgery; 20 had more than 1 surgery. The mean gross tumor volume was 27.6 cm{sup 3}; mean clinical target volume was 52.9 cm{sup 3}. Median totalmore » doses for patients with and without histologic verification were 59 and 57 Gy, respectively. Mean and median follow-up periods were 74 months. Results: The overall 5-year actuarial control rate was 96%; the control rate was 99% in patients with grade 1 or absent histologic findings and 50% for those with atypical histology. All 21 patients who did not have histologic verification and 46 of 47 patients with histologic confirmation of grade 1 tumor demonstrated disease control at 5 years. Control rates for patients without previous surgery, 1 surgery, and 2 or more surgeries were 95%, 96%, and 95%, respectively. Conclusions: Fractionated proton radiotherapy for grade 1 cavernous sinus meningiomas achieves excellent control rates with minimal toxicities, regardless of surgical intervention or use of histologic diagnosis. Disease control for large lesions can be achieved by primary fractionated proton therapy.« less

Proton Pump Inhibitors in Gastroesophageal Reflux Disease: Friend or Foe.

PubMed

Gyawali, C Prakash

2017-09-01

Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.

ON THE BENEFITS AND RISKS OF PROTON THERAPY IN PEDIATRIC CRANIOPHARYNGIOMA

PubMed Central

Beltran, Chris; Roca, Monica; Merchant, Thomas E.

2013-01-01

Purpose Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm3, and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R2 values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Conclusions Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not. PMID:21570209

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

Schulte, R.

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

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.

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.

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

Hata, Masaharu; Tokuuye, Koichi; Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki

Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm)more » in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade {>=}3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.« less

Proton beam irradiation: a safe procedure in post-equatorial extraocular extension from uveal melanoma.

PubMed

Seibel, Ira; Riechardt, Aline I; Erb-Eigner, Katharina; Böker, Alexander; Cordini, Dino; Heufelder, Jens; Joussen, Antonia M

2018-04-12

This study was performed to show long-term outcomes concerning metastasis rates and local recurrence rates after primary proton beam therapy in uveal melanoma with posterior extraocular extension (EOE) with the main focus on optic nerve invasion. Retrospective case series METHODS: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma with posterior EOE between July 1998 and August 2010 were included. EOE was either detected upon sonography at primary examination or during the surgical application of tantalum clips onto the sclera. Ultrasound was performed in each patient before surgery, and if EOE was detected, a magnetic resonance imaging (MRI) scan was performed to confirm EOE. All patients with tumors exceeding 6 mm in thickness or abutting the optic disc received a 1.5 Tesla MRI scan after clip surgery. To asses EOE during follow-up, either ultrasound examinations or-if initially detected only by MRI-MRI scans were performed during follow-up. A total of 27 patients underwent primary proton beam therapy. The EOE was separated into 3 growth types: Optic nerve infiltration in 10 patients, vortex vein infiltration in 9 patients, and transscleral growth post-equatorially in 8 patients. No local recurrences were found during the overall median follow-up of 80 months (11-168 months). Metastasis rates correlated with AJCC stages but not EOE volume. This study shows that posterior EOE can safely be treated by proton beam therapy, even if the optic nerve is infiltrated. MRI enables safe detection of optic nerve invasion. Copyright © 2018 Elsevier Inc. All rights reserved.

Proton Therapy

MedlinePlus

... matter is made up of tiny particles called atoms. At the center of every atom is a nucleus, which holds two types of ... which is a nuclear reactor that can smash atoms to release proton, neutron, and helium ion beams. ...

The Durability of Endoscopic Therapy for Treatment of Barrett's Metaplasia, Dysplasia, and Mucosal Cancer After Nissen Fundoplication.

PubMed

Johnson, Corey S; Louie, Brian E; Wille, Aaron; Dunst, Christy M; Worrell, Stephanie G; DeMeester, Steven R; Reynolds, Jessica; Dixon, Joe; Lipham, John C; Lada, Michal; Peters, Jeffrey H; Watson, Thomas J; Farivar, Alexander S; Aye, Ralph W

2015-05-01

Radiofrequency ablation (RFA) ± endoscopic resection (EMR) is an established treatment strategy for neoplastic Barrett's and intramucosal cancer. Most patients are managed with proton pump inhibitors. The incidence of recurrent Barrett's metaplasia, dysplasia, or cancer after complete eradication is up to 43 % using this strategy. We hypothesize the addition of fundoplication should result in a lower recurrence rates after complete eradication. Multi-institutional retrospective review of patients undergoing endotherapy followed by Nissen fundoplication A total of 49 patients underwent RFA ± EMR followed by Nissen fundoplication. Complete remission of intestinal metaplasia (CR-IM) was achieved in 26 (53 %) patients, complete remission of dysplasia (CR-D) in 16 (33 %) patients, and 7 (14 %) had persistent neoplastic Barrett's. After fundoplication, 18/26 (70 %) remained in CR-IM. An additional 10/16 CR-D achieved CR-IM and 4/7 with persistent dysplasia achieved CR-IM. One patient progressed to LGD while no patient developed HGD or cancer. Endoscopic therapy for Barrett's dysplasia and/or intramucosal cancer followed by fundoplication results in similar durability of CR-IM to patients being managed with PPIs alone after endoscopic therapy. However, fundoplication may be superior in preventing further progression of disease and the development of cancer. Fundoplication is an important strategy to achieve and maintain CR-IM, and facilitate eradication of persistent dysplasia.

The Radiobiology of Proton Therapy: Challenges and Opportunities Around Relative Biological Effectiveness.

PubMed

Jones, B; McMahon, S J; Prise, K M

2018-05-01

With the current UK expansion of proton therapy there is a great opportunity for clinical oncologists to develop a translational interest in the associated scientific base and clinical results. In particular, the underpinning controversy regarding the conversion of photon dose to proton dose by the relative biological effectiveness (RBE) must be understood, including its important implications. At the present time, the proton prescribed dose includes an RBE of 1.1 regardless of tissue, tumour and dose fractionation. A body of data has emerged against this pragmatic approach, including a critique of the existing evidence base, due to choice of dose, use of only acute-reacting in vivo assays, analysis methods and the reference radiations used to determine the RBE. Modelling systems, based on the best available scientific evidence, and which include the clinically useful biological effective dose (BED) concept, have also been developed to estimate proton RBEs for different dose and linear energy transfer (LET) values. The latter reflect ionisation density, which progressively increases along each proton track. Late-reacting tissues, such as the brain, where α/β = 2 Gy, show a higher RBE than 1.1 at a low dose per fraction (1.2-1.8 Gy) at LET values used to cover conventional target volumes and can be much higher. RBE changes with tissue depth seem to vary depending on the method of beam delivery used. To reduce unexpected toxicity, which does occasionally follow proton therapy, a more rational approach to RBE allocation, using a variable RBE that depends on dose per fraction and the tissue and tumour radiobiological characteristics such as α/β, is proposed. Copyright © 2018. Published by Elsevier Ltd.

Two-dimensional silicon-based detectors for ion beam therapy

NASA Astrophysics Data System (ADS)

Martišíková, M.; Granja, C.; Jakůbek, J.; Hartmann, B.; Telsemeyer, J.; Huber, L.; Brons, S.; Pospíšil, S.; Jäkel, O.

2012-02-01

Radiation therapy with ion beams is a highly precise kind of cancer treatment. As ion beams traverse material, the highest ionization density occurs at the end of their path. Due to this Bragg-peak, ion beams enable higher dose conformation to the tumor and increased sparing of the surrounding tissue, in comparison to standard radiation therapy using high energy photons. Ions heavier than protons offer in addition increased biological effectiveness and lower scattering. The Heidelberg Ion Beam Therapy Center (HIT) is a state-of-the-art ion beam therapy facility and the first hospital-based facility in Europe. It provides proton and carbon ion treatments. A synchrotron is used for ion acceleration. For dose delivery to the patient, narrow pencil-like beams are scanned over the target volume.

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

Feasibility study of proton-based quality assurance of proton range compensator

NASA Astrophysics Data System (ADS)

Park, S.; Jeong, C.; Min, B. J.; Kwak, J.; Lee, J.; Cho, S.; Shin, D.; Lim, Y. K.; Park, S. Y.; Lee, S. B.

2013-06-01

All patient specific range compensators (RCs) are customized for achieving distal dose conformity of target volume in passively scattered proton therapy. Compensators are milled precisely using a computerized machine. In proton therapy, precision of the compensator is critical and quality assurance (QA) is required to protect normal tissues and organs from radiation damage. This study aims to evaluate the precision of proton-based quality assurance of range compensator. First, the geometry information of two compensators was extracted from the DICOM Radiotherapy (RT) plan. Next, RCs were irradiated on the EBT film individually by proton beam which is modulated to have a photon-like percent depth dose (PDD). Step phantoms were also irradiated on the EBT film to generate calibration curve which indicates relationship between optical density of irradiated film and perpendicular depth of compensator. Comparisons were made using the mean absolute difference (MAD) between coordinate information from DICOM RT and converted depth information from the EBT film. MAD over the whole region was 1.7, and 2.0 mm. However, MAD over the relatively flat regions on each compensator selected for comparison was within 1 mm. These results shows that proton-based quality assurance of range compensator is feasible and it is expected to achieve MAD over the whole region less than 1 mm with further correction about scattering effect of proton imaging.

[Influence of proton pump inhibitors on intestinal fermentative profile: a case-control study].

PubMed

Senderovky, Melisa; Lasa, Juan; Dima, Guillermo; Peralta, Daniel; Argüello, Mariano; Soifer, Luis

2014-01-01

Proton pump inhibitors could have an impact on the results of breath tests performed in patients with irritable bowel syndrome. This impact could be due to the development of small intestine bacterial overgrowth. To compare the prevalence of fermentative profile alterations of irritable bowel syndrome patients exposed and not-exposed to proton pump inhibitor therapy. Subjects with irritable bowel syndrome were enrolled. A validated questionnaire assessing symptom severity as well as proton pump inhibitor treatment was delivered. A lactulose breath test was undertaken by each enrolled subject. Fermentative profile (area under the curve of hydrogen excretion/time) was compared between proton pump inhibitors consumers and non-consumers. Furthermore, small intestine bacterial overgrowth prevalence was compared. Two hundred and twenty five patients were enrolled. No significant differences were found on the fermentative profile between groups [AUC mediana 3,776 (rango 2,124-5,571) vs 4,347 (rango 2,038-5,481), P = 0.3]. Small intestine bacterial overgrowth prevalence was similar as well [33% vs 27.5%]. These differences remained non-significant after adjusting for proton pump inhibitor dose and treatment time. Surprisingly, symptom score was significantly higher in those patients under proton pump inhibitor therapy [28.5 (23-26) vs 23 (15-29), P = 0.01]. Proton pump inhibitors have no significant influence on lactulose breath tests, regardless of the dosage and time of administration.

Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial.

PubMed

Eekers, Daniëlle B P; Roelofs, Erik; Jelen, Urszula; Kirk, Maura; Granzier, Marlies; Ammazzalorso, Filippo; Ahn, Peter H; Janssens, Geert O R J; Hoebers, Frank J P; Friedmann, Tobias; Solberg, Timothy; Walsh, Sean; Troost, Esther G C; Kaanders, Johannes H A M; Lambin, Philippe

2016-12-01

In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D 2 ) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Proton Radiotherapy for Solid Tumors of Childhood

PubMed Central

Cotter, Shane E.; McBride, Sean M.; Yock, Torunn I.

2012-01-01

The increasing efficacy of pediatric cancer therapy over the past four decades has produced many long-term survivors that now struggle with serious treatment related morbidities affecting their quality of life. Radiation therapy is responsible for a significant proportion of these late effects, but a relatively new and emerging modality, proton radiotherapy hold great promise to drastically reduce these treatment related late effects in long term survivors by sparing dose to normal tissues. Dosimetric studies of proton radiotherapy compared with best available photon based treatment show significant dose sparing to developing normal tissues. Furthermore, clinical data are now emerging that begin to quantify the benefit in decreased late treatment effects while maintaining excellent cancer control rates. PMID:22417062

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.

Software platform for simulation of a prototype proton CT scanner.

PubMed

Giacometti, Valentina; Bashkirov, Vladimir A; Piersimoni, Pierluigi; Guatelli, Susanna; Plautz, Tia E; Sadrozinski, Hartmut F-W; Johnson, Robert P; Zatserklyaniy, Andriy; Tessonnier, Thomas; Parodi, Katia; Rosenfeld, Anatoly B; Schulte, Reinhard W

2017-03-01

Proton computed tomography (pCT) is a promising imaging technique to substitute or at least complement x-ray CT for more accurate proton therapy treatment planning as it allows calculating directly proton relative stopping power from proton energy loss measurements. A proton CT scanner with a silicon-based particle tracking system and a five-stage scintillating energy detector has been completed. In parallel a modular software platform was developed to characterize the performance of the proposed pCT. The modular pCT software platform consists of (1) a Geant4-based simulation modeling the Loma Linda proton therapy beam line and the prototype proton CT scanner, (2) water equivalent path length (WEPL) calibration of the scintillating energy detector, and (3) image reconstruction algorithm for the reconstruction of the relative stopping power (RSP) of the scanned object. In this work, each component of the modular pCT software platform is described and validated with respect to experimental data and benchmarked against theoretical predictions. In particular, the RSP reconstruction was validated with both experimental scans, water column measurements, and theoretical calculations. The results show that the pCT software platform accurately reproduces the performance of the existing prototype pCT scanner with a RSP agreement between experimental and simulated values to better than 1.5%. The validated platform is a versatile tool for clinical proton CT performance and application studies in a virtual setting. The platform is flexible and can be modified to simulate not yet existing versions of pCT scanners and higher proton energies than those currently clinically available. © 2017 American Association of Physicists in Medicine.

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.

Medical Therapy for Cushing's Syndrome in the Twenty-first Century.

PubMed

Tritos, Nicholas A; Biller, Beverly M K

2018-06-01

Medical therapy has a useful adjunctive role in many patients with Cushing's syndrome. Patients with pituitary corticotroph adenomas who have received radiation therapy to the sella require medical therapy until the effects of radiation therapy occur. In addition, patients with Cushing's syndrome who cannot undergo surgery promptly, including those who are acutely ill and cannot safely undergo tumor resection, may benefit from medical therapy as a bridge to surgery. Other possible candidates for medical therapy are those with unresectable tumors or those whose tumor location remains unknown despite adequate diagnostic evaluation. Copyright © 2018 Elsevier Inc. All rights reserved.

Status of hadron therapy in Europe and the role of ENLIGHT

NASA Astrophysics Data System (ADS)

Dosanjh, Manjit; Hoffmann, Hans Falk; Magrin, Giulio

2007-02-01

Cancer is a major social problem, and it is the main cause of death between the ages 45-65 years. In the treatment of cancer, radio therapy (RT) plays an essential role. RT with hadrons (protons and light ions), due to their unique physical and radiobiological properties, offers several advantages over photons. In particular, they penetrate the patient with minimal diffusion, they deposit maximum energy at the end of their range, and they can be shaped as narrow focused and scanned pencil beams of variable penetration depth. Hadron beams allow highly conformal treatment (where the beam conforms to the shape of the tumour) of deep-seated tumours with great accuracy, while delivering minimal doses to surrounding tissues. Hadron therapy, thus, has great prospects for being used in early stages of tumour disease not amenable to surgery. It is likely that, besides its more impressive effect on radio-resistant tumours, post-treatment morbidity will be lower in patients treated with hadrons due to the lower dose and toxicity to normal tissues. Visionary physicist and founder of Fermilab, Robert Wilson first proposed the use of hadrons for cancer treatment in 1946. This idea was first put into practise at the Lawrence Berkeley Laboratory (LBL) where 30 patients were treated with protons between 1954 and 1957. Since then the total number of patients treated with hadrons in the world now exceeds 50,000, of which 5000 new patients were treated last year. Several dedicated hospital-based centres with significant capacity for treating patients are now taking the place of the first R&D facilities hosted by the Physics Research Laboratories (e.g. LBL, GSI). Europe is playing a key role in the advancement of light ion therapy facilities with five financed centres using actively scanned carbon ions (of which two are already under construction in Heidelberg and Pavia) and several proton therapy centres which will become operational soon. In the US, three proton therapy centres are running and four more are under construction. In Japan two carbon ion and four proton centres are running and, in the Far East, also Korea and China are investing in hospital-based hadron therapy centres. The European Network for Research in Light-ion Hadron Therapy (ENLIGHT) was established in 2002 to co-ordinate European efforts in radiation therapy using light-ion beams. ENLIGHT has been instrumental in bringing together different European centres to promote hadron therapy, in particular with carbon ions. ENLIGHT created a multidisciplinary platform, uniting traditionally separate communities so that clinicians, physicists, biologists and engineers with experience in ions work together. The success of the network has encouraged the scientific community to promote more inclusive collaboration between the researchers and regional activities and to enlarge the collaboration to include the proton community. Hence, ENLIGHT++ continues the vision started by ENLIGHT.

On the origin of the visible light responsible for proton dose measurement using plastic optical fibers

NASA Astrophysics Data System (ADS)

Darafsheh, Arash; Taleei, Reza; Kassaee, Alireza; Finlay, Jarod C.

2017-03-01

We experimentally and by means of Monte Carlo simulations investigated the origin of the visible signal responsible for proton therapy dose measurement using bare plastic optical fibers. Experimentally, the fiber optic probe, embedded in tissue-mimicking plastics, was irradiated with a proton beam produced by a proton therapy cyclotron and the luminescence spectroscopy was performed by a CCD-coupled spectrograph to analyze the emission spectrum of the fiber tip. Monte Carlo simulations were performed using FLUKA Monte Carlo code to stochastically simulate radiation transport, ionizing radiation dose deposition, and optical emission of Čerenkov radiation. The spectroscopic study of proton-irradiated plastic fibers showed a continuous spectrum with 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. Our results show that the origin of the optical signal responsible for the proton dose measurement using bare optical fibers is not Čerenkov radiation. Our results point toward a connection between the scintillation of the plastic material of the fiber and the origin of the signal responsible for dose measurement.

Is it necessary to plan with safety margins for actively scanned proton therapy?

NASA Astrophysics Data System (ADS)

Albertini, F.; Hug, E. B.; Lomax, A. J.

2011-07-01

In radiation therapy, a plan is robust if the calculated and the delivered dose are in agreement, even in the case of different uncertainties. The current practice is to use safety margins, expanding the clinical target volume sufficiently enough to account for treatment uncertainties. This, however, might not be ideal for proton therapy and in particular when using intensity modulated proton therapy (IMPT) plans as degradation in the dose conformity could also be found in the middle of the target resulting from misalignments of highly in-field dose gradients. Single field uniform dose (SFUD) and IMPT plans have been calculated for different anatomical sites and the need for margins has been assessed by analyzing plan robustness to set-up and range uncertainties. We found that the use of safety margins is a good way to improve plan robustness for SFUD and IMPT plans with low in-field dose gradients but not necessarily for highly modulated IMPT plans for which only a marginal improvement in plan robustness could be detected through the definition of a planning target volume.

Development of the compact proton beam therapy system dedicated to spot scanning with real-time tumor-tracking technology

NASA Astrophysics Data System (ADS)

Umezawa, Masumi; Fujimoto, Rintaro; Umekawa, Tooru; Fujii, Yuusuke; Takayanagi, Taisuke; Ebina, Futaro; Aoki, Takamichi; Nagamine, Yoshihiko; Matsuda, Koji; Hiramoto, Kazuo; Matsuura, Taeko; Miyamoto, Naoki; Nihongi, Hideaki; Umegaki, Kikuo; Shirato, Hiroki

2013-04-01

Hokkaido University and Hitachi Ltd. have started joint development of the Gated Spot Scanning Proton Therapy with Real-Time Tumor-Tracking System by integrating real-time tumor tracking technology (RTRT) and the proton therapy system dedicated to discrete spot scanning techniques under the "Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)". In this development, we have designed the synchrotron-based accelerator system by using the advantages of the spot scanning technique in order to realize a more compact and lower cost proton therapy system than the conventional system. In the gated irradiation, we have focused on the issues to maximize irradiation efficiency and minimize the dose errors caused by organ motion. In order to understand the interplay effect between scanning beam delivery and target motion, we conducted a simulation study. The newly designed system consists of the synchrotron, beam transport system, one compact rotating gantry treatment room with robotic couch, and one experimental room for future research. To improve the irradiation efficiency, the new control function which enables multiple gated irradiations per synchrotron cycle has been applied and its efficacy was confirmed by the irradiation time estimation. As for the interplay effect, we confirmed that the selection of a strict gating width and scan direction enables formation of the uniform dose distribution.

Range verification for eye proton therapy based on proton-induced x-ray emissions from implanted metal markers

NASA Astrophysics Data System (ADS)

La Rosa, Vanessa; Kacperek, Andrzej; Royle, Gary; Gibson, Adam

2014-06-01

Metal fiducial markers are often implanted on the back of the eye before proton therapy to improve target localization and reduce patient setup errors. We aim to detect characteristic x-ray emissions from metal targets during proton therapy to verify the treatment range accuracy. Initially gold was chosen for its biocompatibility properties. Proton-induced x-ray emissions (PIXE) from a 15 mm diameter gold marker were detected at different penetration depths of a 59 MeV proton beam at the CATANA proton facility at INFN-LNS (Italy). The Monte Carlo code Geant4 was used to reproduce the experiment and to investigate the effect of different size markers, materials, and the response to both mono-energetic and fully modulated beams. The intensity of the emitted x-rays decreases with decreasing proton energy and thus decreases with depth. If we assume the range to be the depth at which the dose is reduced to 10% of its maximum value and we define the residual range as the distance between the marker and the range of the beam, then the minimum residual range which can be detected with 95% confidence level is the depth at which the PIXE peak is equal to 1.96 σbkg, which is the standard variation of the background noise. With our system and experimental setup this value is 3 mm, when 20 GyE are delivered to a gold marker of 15 mm diameter. Results from silver are more promising. Even when a 5 mm diameter silver marker is placed at a depth equal to the range, the PIXE peak is 2.1 σbkg. Although these quantitative results are dependent on the experimental setup used in this research study, they demonstrate that the real-time analysis of the PIXE emitted by fiducial metal markers can be used to derive beam range. Further analysis are needed to demonstrate the feasibility of the technique in a clinical setup.

Investigation of EBT2 and EBT3 films for proton dosimetry in the 4-20 MeV energy range.

PubMed

Reinhardt, S; Würl, M; Greubel, C; Humble, N; Wilkens, J J; Hillbrand, M; Mairani, A; Assmann, W; Parodi, K

2015-03-01

Radiochromic films such as Gafchromic EBT2 or EBT3 films are widely used for dose determination in radiation therapy because they offer a superior spatial resolution compared to any other digital dosimetric 2D detector array. The possibility to detect steep dose gradients is not only attractive for intensity-modulated radiation therapy with photons but also for intensity-modulated proton therapy. Their characteristic dose rate-independent response makes radiochromic films also attractive for dose determination in cell irradiation experiments using laser-driven ion accelerators, which are currently being investigated as future medical ion accelerators. However, when using these films in ion beams, the energy-dependent dose response in the vicinity of the Bragg peak has to be considered. In this work, the response of these films for low-energy protons is investigated. To allow for reproducible and background-free irradiation conditions, the films were exposed to mono-energetic protons from an electrostatic accelerator, in the 4-20 MeV energy range. For comparison, irradiation with clinical photons was also performed. It turned out that in general, EBT2 and EBT3 films show a comparable performance. For example, dose-response curves for photons and protons with energies as low as 11 MeV show almost no differences. However, corrections are required for proton energies below 11 MeV. Care has to be taken when correction factors are related to an average LET from depth-dose measurements, because only the dose-averaged LET yields similar results as obtained in mono-energetic measurements.

Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Dosimetric Study

PubMed Central

Kesarwala, Aparna H.; Ko, Christine J.; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E.; O’Meara, William P.; Simone, Charles B.; Rengan, Ramesh

2015-01-01

Background Photon involved-field radiation therapy (IFRT), the standard for locally advanced non-small cell lung cancer (LA-NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Given the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Materials and Methods IMPT IFRT plans were generated to the same total dose of 66.6–72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 CGE to elective nodal (EN) planning treatment volumes (PTV) plus 24 CGE to involved field (IF)-PTVs. Results Proton IFRT and ENI both improved D95 involved field (IF)-PTV coverage by 4% (p<0.01) compared to photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. Lung V20 and mean lung dose decreased 18% (p<0.01) and 36% (p<0.01), respectively, with proton IFRT and 11% (p=0.03) and 26% (p<0.01) with ENI. Mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all p<0.01). Conclusions This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates IMPT could allow ENI while maintaining a favorable therapeutic ratio compared to photon IFRT. PMID:25604729

Intensity-modulated proton therapy for elective nodal irradiation and involved-field radiation in the definitive treatment of locally advanced non-small-cell lung cancer: a dosimetric study.

PubMed

Kesarwala, Aparna H; Ko, Christine J; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E; O'Meara, William P; Simone, Charles B; Rengan, Ramesh

2015-05-01

Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P < .01) compared with photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. The lung percentage of volume receiving 20 Gy/CGE (V20) and mean lung dose decreased 18% (P < .01) and 36% (P < .01), respectively, with proton IFRT, and 11% (P = .03) and 26% (P < .01) with ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P < .01). This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT. Published by Elsevier Inc.

SU-F-T-217: A Comprehensive Monte-Carlo Study of Out-Of-Field Secondary Neutron Spectra in a Scanned-Beam Proton Therapy Treatment Room

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

Englbrecht, F; Parodi, K; Trinkl, S

2016-06-15

Purpose: To simulate secondary neutron radiation-fields produced at different positions during phantom irradiation inside a scanning proton therapy gantry treatment room. Further, to identify origin, energy distribution and angular emission as function of proton beam energy. Methods: GEANT4 and FLUKA Monte-Carlo codes were used to model the relevant parts of the treatment room in a gantry-equipped pencil beam scanning proton therapy facility including walls, floor, metallic gantry-components, patient table and the homogeneous PMMA target. The proton beams were modeled based on experimental beam ranges in water and spot shapes in air. Neutron energy spectra were simulated at 0°, 45°, 90°more » and 135° relative to the beam axis at 2m distance from isocenter, as well as 11×11 cm2 fields for 75MeV, 140MeV, 200MeV and for 118MeV with 5cm PMMA range-shifter. The total neutron energy distribution was recorded for these four positions and proton energies. Additionally, the room-components generating secondary neutrons in the room and their contributions to the total spectrum were identified and quantified. Results: FLUKA and GEANT4 simulated neutron spectra showed good general agreement in the whole energy range of 10{sup −}9 to 10{sup 2} MeV. Comparison of measured spectra with the simulated contributions of the various room components helped to limit the complexity of the room model, by identifying the dominant contributions to the secondary neutron spectrum. The iron of the bending magnet and counterweight were identified as sources of secondary evaporation-neutrons, which were lacking in simplified room models. Conclusion: Thorough Monte-Carlo simulations have been performed to complement Bonner-sphere spectrometry measurements of secondary neutrons in a clinical proton therapy treatment room. Such calculations helped disentangling the origin of secondary neutrons and their dominant contributions to measured spectra, besides providing a useful validation of widely used Monte-Carlo packages in comparison to experimental data. Cluster of Excellence of the German Research Foundation (DFG) “Munich-Centre for Advanced Photonics (MAP)”.« less

Radiation Hardness of dSiPM Sensors in a Proton Therapy Radiation Environment

NASA Astrophysics Data System (ADS)

Diblen, Faruk; Buitenhuis, Tom; Solf, Torsten; Rodrigues, Pedro; van der Graaf, Emiel; van Goethem, Marc-Jan; Brandenburg, Sytze; Dendooven, Peter

2017-07-01

In vivo verification of dose delivery in proton therapy by means of positron emission tomography (PET) or prompt gamma imaging is mostly based on fast scintillation detectors. The digital silicon photomultiplier (dSiPM) allows excellent scintillation detector timing properties and is thus being considered for such verification methods. We present here the results of the first investigation of radiation damage to dSiPM sensors in a proton therapy radiation environment. Radiation hardness experiments were performed at the AGOR cyclotron facility at the KVI-Center for Advanced Radiation Technology, University of Groningen. A 150-MeV proton beam was fully stopped in a water target. In the first experiment, bare dSiPM sensors were placed at 25 cm from the Bragg peak, perpendicular to the beam direction, a geometry typical for an in situ implementation of a PET or prompt gamma imaging device. In the second experiment, dSiPM-based PET detectors containing lutetium yttrium orthosilicate scintillator crystal arrays were placed at 2 and 4 m from the Bragg peak, perpendicular to the beam direction; resembling an in-room PET implementation. Furthermore, the experimental setup was simulated with a Geant4-based Monte Carlo code in order to determine the angular and energy distributions of the neutrons and to determine the 1-MeV equivalent neutron fluences delivered to the dSiPM sensors. A noticeable increase in dark count rate (DCR) after an irradiation with about 108 1-MeV equivalent neutrons/cm2 agrees with observations by others for analog SiPMs, indicating that the radiation damage occurs in the single photon avalanche diodes and not in the electronics integrated on the sensor chip. It was found that in the in situ location, the DCR becomes too large for successful operation after the equivalent of a few weeks of use in a proton therapy treatment room (about 5 × 1013 protons). For PET detectors in an in-room setup, detector performance was unchanged even after an irradiation equivalent to three years of use in a treatment room (3 × 1015 protons).

SU-E-T-594: Out-Of-Field Neutron and Gamma Dose Estimated Using TLD-600/700 Pairs in the Wobbling Proton Therapy System

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

Chen, Y; Lin, Y; Medical Physics Research Center, Institute for Radiological Research, Chang Gung University / Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

Purpose: Secondary fast neutrons and gamma rays are mainly produced due to the interaction of the primary proton beam with the beam delivery nozzle. These secondary radiation dose to patients and radiation workers are unwanted. The purpose of this study is to estimate the neutron and gamma dose equivalent out of the treatment volume during the wobbling proton therapy system. Methods: Two types of thermoluminescent (TL) dosimeters, TLD-600 ({sup 6}LiF: Mg, Ti) and TLD-700 ({sup 7}LiF: Mg, Ti) were used in this study. They were calibrated in the standard neutron and gamma sources at National Standards Laboratory. Annealing procedure ismore » 400°C for 1 hour, 100°C for 2 hours and spontaneously cooling down to the room temperature in a programmable oven. Two-peak method (a kind of glow curve analysis technique) was used to evaluate the TL response corresponding to the neutron and gamma dose. The TLD pairs were placed outside the treatment field at the neutron-gamma mixed field with 190-MeV proton beam produced by the wobbling system through the polyethylene plate phantom. The results of TLD measurement were compared to the Monte Carlo simulation. Results: The initial experiment results of calculated dose equivalents are 0.63, 0.38, 0.21 and 0.13 mSv per Gy outside the field at the distance of 50, 100, 150 and 200 cm. Conclusion: The TLD-600 and TLD-700 pairs are convenient to estimate neutron and gamma dosimetry during proton therapy. However, an accurate and suitable glow curve analysis technique is necessary. During the wobbling system proton therapy, our results showed that the neutron and gamma doses outside the treatment field are noticeable. This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1C0682)« less

Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia.

PubMed

Boban, Marko; Zulj, Marinko; Persic, Viktor; Medved, Igor; Zekanovic, Drazen; Vcev, Aleksandar

2016-09-15

Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. The study included consecutive patients scheduled for cardiovascular rehabilitation 2-6months after index cardiovascular treatment. Two hundred ninety-four patients (n=294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05-8.22; p<0.001) and PCI 0.15 (CI: 0.10-0.22; p<0.001). The odds for having proton pump inhibitor in their chronic therapy were increased for atrial fibrillation 1.87 (CI: 1.08-3.23; p=0.025) and decreased for obesity 0.65 (CI: 0.45-0.96; p=0.035); surviving myocardial infarction 0.49 (CI: 0.29-0.83; p=0.035). Multinomial logistic regression controlled for existence of chronic renal disease found no significant association of renal dysfunction and PPI therapy. The existence of anemia was significantly increased in patients taking PPIs than controls; 6.00 (CI: 3.85-9.33; p<0.001). The use of PPI was also associated with worsening of metabolic profile, in part due to decreased utilization of ACE-inhibitors and statins. PPI consumption correlated with age of patients (Rho=0.216; p<0.001). High proportion of cardiovascular, particularly surgical patients with ischemic and valvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

TH-A-19A-11: Validation of GPU-Based Monte Carlo Code (gPMC) Versus Fully Implemented Monte Carlo Code (TOPAS) for Proton Radiation Therapy: Clinical Cases Study

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

Giantsoudi, D; Schuemann, J; Dowdell, S

Purpose: For proton radiation therapy, Monte Carlo simulation (MCS) methods are recognized as the gold-standard dose calculation approach. Although previously unrealistic due to limitations in available computing power, GPU-based applications allow MCS of proton treatment fields to be performed in routine clinical use, on time scales comparable to that of conventional pencil-beam algorithms. This study focuses on validating the results of our GPU-based code (gPMC) versus fully implemented proton therapy based MCS code (TOPAS) for clinical patient cases. Methods: Two treatment sites were selected to provide clinical cases for this study: head-and-neck cases due to anatomical geometrical complexity (air cavitiesmore » and density heterogeneities), making dose calculation very challenging, and prostate cases due to higher proton energies used and close proximity of the treatment target to sensitive organs at risk. Both gPMC and TOPAS methods were used to calculate 3-dimensional dose distributions for all patients in this study. Comparisons were performed based on target coverage indices (mean dose, V90 and D90) and gamma index distributions for 2% of the prescription dose and 2mm. Results: For seven out of eight studied cases, mean target dose, V90 and D90 differed less than 2% between TOPAS and gPMC dose distributions. Gamma index analysis for all prostate patients resulted in passing rate of more than 99% of voxels in the target. Four out of five head-neck-cases showed passing rate of gamma index for the target of more than 99%, the fifth having a gamma index passing rate of 93%. Conclusion: Our current work showed excellent agreement between our GPU-based MCS code and fully implemented proton therapy based MC code for a group of dosimetrically challenging patient cases.« less

A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas.

PubMed

Thompson, Reid F; Mayekar, Sonal U; Zhai, Huifang; Both, Stefan; Apisarnthanarax, Smith; Metz, James M; Plastaras, John P; Ben-Josef, Edgar

2014-08-01

Uncontrolled local growth is the cause of death in ∼ 30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6-53.8 and 34.9-52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

Proton Minibeam Radiation Therapy Reduces Side Effects in an In Vivo Mouse Ear Model

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

Girst, Stefanie, E-mail: stefanie.girst@unibw.de; Greubel, Christoph; Reindl, Judith

Purpose: 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. Methods andmore » Materials: At the ion microprobe SNAKE, 20-MeV protons were administered to the central part (7.2 × 7.2 mm{sup 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{sup 2}, with a distance of 1.8 mm). The same average dose was used over the irradiated area. Results: 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. Conclusions: 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.« less

Accuracy of parameterized proton range models; A comparison

NASA Astrophysics Data System (ADS)

Pettersen, H. E. S.; Chaar, M.; Meric, I.; Odland, O. H.; Sølie, J. R.; Röhrich, D.

2018-03-01

An accurate calculation of proton ranges in phantoms or detector geometries is crucial for decision making in proton therapy and proton imaging. To this end, several parameterizations of the range-energy relationship exist, with different levels of complexity and accuracy. In this study we compare the accuracy of four different parameterizations models for proton range in water: Two analytical models derived from the Bethe equation, and two different interpolation schemes applied to range-energy tables. In conclusion, a spline interpolation scheme yields the highest reproduction accuracy, while the shape of the energy loss-curve is best reproduced with the differentiated Bragg-Kleeman equation.

Secondary neutron spectrum from 250-MeV passively scattered proton therapy: measurement with an extended-range Bonner sphere system.

PubMed

Howell, Rebecca M; Burgett, E A

2014-09-01

Secondary neutrons are an unavoidable consequence of proton therapy. While the neutron dose is low compared to the primary proton dose, its presence and contribution to the patient dose is nonetheless important. The most detailed information on neutrons includes an evaluation of the neutron spectrum. However, the vast majority of the literature that has reported secondary neutron spectra in proton therapy is based on computational methods rather than measurements. This is largely due to the inherent limitations in the majority of neutron detectors, which are either not suitable for spectral measurements or have limited response at energies greater than 20 MeV. Therefore, the primary objective of the present study was to measure a secondary neutron spectrum from a proton therapy beam using a spectrometer that is sensitive to neutron energies over the entire neutron energy spectrum. The authors measured the secondary neutron spectrum from a 250-MeV passively scattered proton beam in air at a distance of 100 cm laterally from isocenter using an extended-range Bonner sphere (ERBS) measurement system. Ambient dose equivalent H*(10) was calculated using measured fluence and fluence-to-ambient dose equivalent conversion coefficients. The neutron fluence spectrum had a high-energy direct neutron peak, an evaporation peak, a thermal peak, and an intermediate energy continuum between the thermal and evaporation peaks. The H*(10) was dominated by the neutrons in the evaporation peak because of both their high abundance and the large quality conversion coefficients in that energy interval. The H*(10) 100 cm laterally from isocenter was 1.6 mSv per proton Gy (to isocenter). Approximately 35% of the dose equivalent was from neutrons with energies ≥20 MeV. The authors measured a neutron spectrum for external neutrons generated by a 250-MeV proton beam using an ERBS measurement system that was sensitive to neutrons over the entire energy range being measured, i.e., thermal to 250 MeV. The authors used the neutron fluence spectrum to demonstrate experimentally the contribution of neutrons with different energies to the total dose equivalent and in particular the contribution of high-energy neutrons (≥20 MeV). These are valuable reference data that can be directly compared with Monte Carlo and experimental data in the literature.

Secondary neutron spectrum from 250-MeV passively scattered proton therapy: Measurement with an extended-range Bonner sphere system

PubMed Central

Howell, Rebecca M.; Burgett, E. A.

2014-01-01

Purpose: Secondary neutrons are an unavoidable consequence of proton therapy. While the neutron dose is low compared to the primary proton dose, its presence and contribution to the patient dose is nonetheless important. The most detailed information on neutrons includes an evaluation of the neutron spectrum. However, the vast majority of the literature that has reported secondary neutron spectra in proton therapy is based on computational methods rather than measurements. This is largely due to the inherent limitations in the majority of neutron detectors, which are either not suitable for spectral measurements or have limited response at energies greater than 20 MeV. Therefore, the primary objective of the present study was to measure a secondary neutron spectrum from a proton therapy beam using a spectrometer that is sensitive to neutron energies over the entire neutron energy spectrum. Methods: The authors measured the secondary neutron spectrum from a 250-MeV passively scattered proton beam in air at a distance of 100 cm laterally from isocenter using an extended-range Bonner sphere (ERBS) measurement system. Ambient dose equivalent H*(10) was calculated using measured fluence and fluence-to-ambient dose equivalent conversion coefficients. Results: The neutron fluence spectrum had a high-energy direct neutron peak, an evaporation peak, a thermal peak, and an intermediate energy continuum between the thermal and evaporation peaks. The H*(10) was dominated by the neutrons in the evaporation peak because of both their high abundance and the large quality conversion coefficients in that energy interval. The H*(10) 100 cm laterally from isocenter was 1.6 mSv per proton Gy (to isocenter). Approximately 35% of the dose equivalent was from neutrons with energies ≥20 MeV. Conclusions: The authors measured a neutron spectrum for external neutrons generated by a 250-MeV proton beam using an ERBS measurement system that was sensitive to neutrons over the entire energy range being measured, i.e., thermal to 250 MeV. The authors used the neutron fluence spectrum to demonstrate experimentally the contribution of neutrons with different energies to the total dose equivalent and in particular the contribution of high-energy neutrons (≥20 MeV). These are valuable reference data that can be directly compared with Monte Carlo and experimental data in the literature. PMID:25186404

Myofunctional therapy improves adherence to continuous positive airway pressure treatment.

PubMed

Diaféria, Giovana; Santos-Silva, Rogerio; Truksinas, Eveli; Haddad, Fernanda L M; Santos, Renata; Bommarito, Silvana; Gregório, Luiz C; Tufik, Sergio; Bittencourt, Lia

2017-05-01

Few studies have investigated myofunctional therapy in patients with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the effect of myofunctional therapy on continuous positive airway pressure (CPAP) adherence. The study was registered at ClinicalTrials.gov (NCT01289405). Male patients with OSAS were randomly divided into four treatment groups: placebo, patients undergoing placebo myofunctional therapy (N = 24); myofunctional therapy, undergoing myofunctional therapy (N = 27); CPAP, undergoing treatment with CPAP (N = 27); and combined, undergoing CPAP therapy and myofunctional therapy (N = 22). All patients underwent evaluations before and after 3 months of treatment evaluation and after 3 weeks of washout. Evaluations included Epworth sleepiness scale (ESS), polysomnography, and myofunctional evaluation. The 100 men had a mean age of 48.1 ± 11.2 years, body mass index of 27.4 ± 4.9 kg/m 2 , ESS score of 12.7 ± 3.0, and apnea-hypopnea index (AHI) of 30.9 ± 20.6. All treated groups (myofunctional therapy, CPAP, and combined myofunctional therapy with CPAP) showed decreased ESS and snoring, and the myofunctional therapy group maintained this improvement after the "washout" period. AHI reduction occurred in all treated groups and was more significant in CPAP group. The myofunctional therapy and combined groups showed improvement in tongue and soft palate muscle strength when compared with the placebo group. The association of myofunctional therapy to CPAP (combined group) showed an increased adherence to CPAP compared with the CPAP group. Our results suggest that in patients with OSAS, myofunctional therapy may be considered as an adjuvant treatment and an intervention strategy to support adherence to CPAP.

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

Phan, Jack; Sio, Terence T.; Department of Radiation Oncology, Mayo Clinic, Scottsdale, Arizona

Purpose: Reirradiation of head and neck (H&N) cancer is a clinical challenge. Proton radiation therapy (PRT) offers dosimetric advantages for normal tissue sparing and may benefit previously irradiated patients. Here, we report our initial experience with the use of PRT for H&N reirradiation, with focus on clinical outcomes and toxicity. Methods and Materials: We retrospectively reviewed the records of patients who received H&N reirradiation with PRT from April 2011 through June 2015. Patients reirradiated with palliative intent or without prior documentation of H&N radiation therapy were excluded. Radiation-related toxicities were recorded according to the Common Terminology Criteria for Adverse Eventsmore » Version 4.0. Results: The conditions of 60 patients were evaluated, with a median follow-up time of 13.6 months. Fifteen patients (25%) received passive scatter proton therapy (PSPT), and 45 (75%) received intensity modulated proton therapy (IMPT). Thirty-five patients (58%) received upfront surgery, and 44 (73%) received concurrent chemotherapy. The 1-year rates of locoregional failure–free survival, overall survival, progression-free survival, and distant metastasis–free survival were 68.4%, 83.8%, 60.1%, and 74.9%, respectively. Eighteen patients (30%) experienced acute grade 3 (G3) toxicity, and 13 (22%) required a feeding tube at the end of PRT. The 1-year rates of late G3 toxicity and feeding tube independence were 16.7% and 2.0%, respectively. Three patients may have died of reirradiation-related effects (1 acute and 2 late). Conclusions: Proton beam therapy can be a safe and effective curative reirradiation strategy, with acceptable rates of toxicity and durable disease control.« less

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

A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy.

PubMed

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2017-01-07

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

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

Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.

Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities weremore » estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton therapy in the treatment of sinonasal malignancy.« less

A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy

NASA Astrophysics Data System (ADS)

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2017-01-01

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

A New Approach to Integrate GPU-based Monte Carlo Simulation into Inverse Treatment Plan Optimization for Proton Therapy

PubMed Central

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2016-01-01

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6±15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size. PMID:27991456

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

Patterns of Failure in Pediatric Rhabdomyosarcoma After Proton Therapy

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

Vern-Gross, Tamara Z.; Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org; Bradley, Julie A.

Purpose: To report on the patterns of failure in children with rhabdomyosarcoma treated with proton therapy. Patients and Methods: Between February 2007 and November 2013, 66 children with a median age of 4.1 years (range, 0.6-15.3 years) diagnosed with nonmetastatic rhabdomyosarcoma were treated with proton therapy. Clinical target volume 1 was defined as the prechemotherapy tumor plus a 1-cm anatomically constrained margin. Clinical target volume 2 was defined as the postchemotherapy tumor (or tumor bed) plus a 0.5-cm anatomically constrained margin, further expanded to encompass potential pathways of spread, including soft tissue infiltrated with tumor at diagnosis. Results: Of the 66 children,more » 11 developed locally progressive disease at a median of 16 months (range, 14-32 months), for an actuarial 2-year local control rate of 88%. Among the children who progressed, median age and tumor size at diagnosis were 6.7 years (range, 0.6-16 years) and 6 cm (range, 2-8 cm), respectively. Of the recurrences, 64% and 36% were embryonal and alveolar, respectively. Disease progression was observed in 7 (64%) parameningeal, 2 (18%) head and neck (other), and 2 (18%) bladder/prostate subsites. At diagnosis, 8 of 11 patients who developed a recurrence were Intergroup Rhabdomyosarcoma Study stage 3, and all 11 were group III. Of the relapses, 100% (11 of 11) were confirmed as in-field within the composite 95% isodose line. One of the 11 patients (9%) developed a new simultaneous regional nodal recurrence outside of the previously treated radiation field. Conclusion: Early data suggest that the sharp dosimetric gradient associated with proton therapy is not associated with an increased risk of marginal failure. Routine use of a 0.5- to 1-cm clinical target volume 1/2 margin with highly conformal proton therapy does not compromise local control in children diagnosed with rhabdomyosarcoma with unfavorable risk features.« less

Epithermal neutron beams from the 7 Li(p,n) reaction near the threshold for neutron capture therapy

NASA Astrophysics Data System (ADS)

Porras, I.; Praena, J.; Arias de Saavedra, F.; Pedrosa, M.; Esquinas, P.; L. Jiménez-Bonilla, P.

2016-11-01

Two applications for neutron capture therapy of epithermal neutron beams calculated from the 7Li ( p , n reaction are discussed. In particular, i) for a proton beam of 1920 keV of a 30 mA, a neutron beam of adequate features for BNCT is found at an angle of 80° from the forward direction; and ii) for a proton beam of 1910 keV, a neutron beam is obtained at the forward direction suitable for performing radiobiology experiments for the determination of the biological weighting factors of the fast dose component in neutron capture therapy.

The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

PubMed Central

Hussain, Zilla H; Henderson, Emily E; Maradey-Romerao, Carla; George, Nina; Fass, Ronnie; Lacy, Brian E

2015-01-01

Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID:26270485

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy.

PubMed

Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Supuran, Claudiu T; Fais, Stefano

2017-12-23

Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na⁺/H⁺ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities compared with unicellular microorganisms. These systems are also involved in the unresponsiveness or resistance to chemotherapy, leading to the protection of cancer cells from the vast majority of drugs, that when protonated in the acidic tumor microenvironment, do not enter into cancer cells. Indeed, as usually occurs in the progression versus malignancy, resistant tumor clones emerge and proliferate, following a transient initial response to a therapy, thus giving rise to more malignant behavior and rapid tumor progression. Recent studies are supporting the use of a cocktail of proton exchanger inhibitors as a new strategy against cancer.

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy

PubMed Central

Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Fais, Stefano

2017-01-01

Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na+/H+ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities compared with unicellular microorganisms. These systems are also involved in the unresponsiveness or resistance to chemotherapy, leading to the protection of cancer cells from the vast majority of drugs, that when protonated in the acidic tumor microenvironment, do not enter into cancer cells. Indeed, as usually occurs in the progression versus malignancy, resistant tumor clones emerge and proliferate, following a transient initial response to a therapy, thus giving rise to more malignant behavior and rapid tumor progression. Recent studies are supporting the use of a cocktail of proton exchanger inhibitors as a new strategy against cancer. PMID:29295495

Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study.

PubMed

Feuvret, Loïc; Bracci, Stefano; Calugaru, Valentin; Bolle, Stéphanie; Mammar, Hamid; De Marzi, Ludovic; Bresson, Damien; Habrand, Jean-Louis; Mazeron, Jean-Jacques; Dendale, Rémi; Noël, Georges

2016-05-01

Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

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

Zenda, Sadamoto, E-mail: szenda@east.ncc.go.jp; Kawashima, Mitsuhiko; Nishio, Teiji

2011-09-01

Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7;more » and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.« less

Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients.

PubMed

Ling, Ted C; Slater, Jerry M; Nookala, Prashanth; Mifflin, Rachel; Grove, Roger; Ly, Anh M; Patyal, Baldev; Slater, Jerry D; Yang, Gary Y

2014-12-05

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study

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

Feuvret, Loïc, E-mail: loic.feuvret@psl.aphp.fr; Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d'Orsay; Bracci, Stefano

Purpose: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). Methods and Materials: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE];more » range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. Results: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Conclusions: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.« less

Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

PubMed Central

Ling, Ted C.; Slater, Jerry M.; Nookala, Prashanth; Mifflin, Rachel; Grove, Roger; Ly, Anh M.; Patyal, Baldev; Slater, Jerry D.; Yang, Gary Y.

2014-01-01

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients. PMID:25489937

Poster — Thur Eve — 45: Comparison of different Monte Carlo methods of scoring linear energy transfer in modulated proton therapy beams

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

Granville, DA; Sawakuchi, GO

2014-08-15

In this work, we demonstrate inconsistencies in commonly used Monte Carlo methods of scoring linear energy transfer (LET) in proton therapy beams. In particle therapy beams, the LET is an important parameter because the relative biological effectiveness (RBE) depends on it. LET is often determined using Monte Carlo techniques. We used a realistic Monte Carlo model of a proton therapy nozzle to score proton LET in spread-out Bragg peak (SOBP) depth-dose distributions. We used three different scoring and calculation techniques to determine average LET at varying depths within a 140 MeV beam with a 4 cm SOBP and a 250more » MeV beam with a 10 cm SOBP. These techniques included fluence-weighted (Φ-LET) and dose-weighted average (D-LET) LET calculations from: 1) scored energy spectra converted to LET spectra through a lookup table, 2) directly scored LET spectra and 3) accumulated LET scored ‘on-the-fly’ during simulations. All protons (primary and secondary) were included in the scoring. Φ-LET was found to be less sensitive to changes in scoring technique than D-LET. In addition, the spectral scoring methods were sensitive to low-energy (high-LET) cutoff values in the averaging. Using cutoff parameters chosen carefully for consistency between techniques, we found variations in Φ-LET values of up to 1.6% and variations in D-LET values of up to 11.2% for the same irradiation conditions, depending on the method used to score LET. Variations were largest near the end of the SOBP, where the LET and energy spectra are broader.« less

Dosimetric study of uniform scanning proton therapy planning for prostate cancer patients with a metal hip prosthesis, and comparison with volumetric‐modulated arc therapy

PubMed Central

Cheng, ChihYao; Zheng, Yuanshui; Hsi, Wen; Zeidan, Omar; Schreuder, Niek; Vargas, Carlos; Larson, Gary

2014-01-01

The main purposes of this study were to 1) investigate the dosimetric quality of uniform scanning proton therapy planning (USPT) for prostate cancer patients with a metal hip prosthesis, and 2) compare the dosimetric results of USPT with that of volumetric‐modulated arc therapy (VMAT). Proton plans for prostate cancer (four cases) were generated in XiO treatment planning system (TPS). The beam arrangement in each proton plan consisted of three fields (two oblique fields and one lateral or slightly angled field), and the proton beams passing through a metal hip prosthesis was avoided. Dose calculations in proton plans were performed using the pencil beam algorithm. From each proton plan, planning target volume (PTV) coverage value (i.e., relative volume of the PTV receiving the prescription dose of 79.2 CGE) was recorded. The VMAT prostate planning was done using two arcs in the Eclipse TPS utilizing 6 MV X‐rays, and beam entrance through metallic hip prosthesis was avoided. Dose computation in the VMAT plans was done using anisotropic analytical algorithm, and calculated VMAT plans were then normalized such that the PTV coverage in the VMAT plan was the same as in the proton plan of the corresponding case. The dose‐volume histograms of calculated treatment plans were used to evaluate the dosimetric quality of USPT and VMAT. In comparison to the proton plans, on average, the maximum and mean doses to the PTV were higher in the VMAT plans by 1.4% and 0.5%, respectively, whereas the minimum PTV dose was lower in the VMAT plans by 3.4%. The proton plans had lower (or better) average homogeneity index (HI) of 0.03 compared to the one for VMAT (HI = 0.04). The relative rectal volume exposed to radiation was lower in the proton plan, with an average absolute difference ranging from 0.1% to 32.6%. In contrast, using proton planning, the relative bladder volume exposed to radiation was higher at high‐dose region with an average absolute difference ranging from 0.4% to 0.8%, and lower at low‐ and medium‐dose regions with an average absolute difference ranging from 2.7% to 10.1%. The average mean dose to the rectum and bladder was lower in the proton plans by 45.1% and 22.0%, respectively, whereas the mean dose to femoral head was lower in VMAT plans by an average difference of 79.6%. In comparison to the VMAT, the proton planning produced lower equivalent uniform dose (EUD) for the rectum (43.7 CGE vs. 51.4 Gy) and higher EUD for the femoral head (16.7 CGE vs. 9.5 Gy), whereas both the VMAT and proton planning produced comparable EUDs for the prostate tumor (76.2 CGE vs. 76.8 Gy) and bladder (50.3 CGE vs. 51.1 Gy). The results presented in this study show that the combination of lateral and oblique fields in USPT planning could potentially provide dosimetric advantage over the VMAT for prostate cancer involving a metallic hip prosthesis. PACS number: 87.55.D‐, 87.55.ne, 87.55.dk PMID:24892333

Team Update on North American Proton Facilities for Radiation Testing

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.; Turflinger, Thomas; Haas, Thurman; George, Jeffrey; Moss, Steven; Davis, Scott; Kostic, Andrew; Wie, Brian; Reed, Robert; Guertin, Steven;

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

Optimization of GATE and PHITS Monte Carlo code parameters for spot scanning proton beam based on simulation with FLUKA general-purpose code

NASA Astrophysics Data System (ADS)

Kurosu, Keita; Das, Indra J.; Moskvin, Vadim P.

2016-01-01

Spot scanning, owing to its superior dose-shaping capability, provides unsurpassed dose conformity, in particular for complex targets. However, the robustness of the delivered dose distribution and prescription has to be verified. Monte Carlo (MC) simulation has the potential to generate significant advantages for high-precise particle therapy, especially for medium containing inhomogeneities. However, the inherent choice of computational parameters in MC simulation codes of GATE, PHITS and FLUKA that is observed for uniform scanning proton beam needs to be evaluated. This means that the relationship between the effect of input parameters and the calculation results should be carefully scrutinized. The objective of this study was, therefore, to determine the optimal parameters for the spot scanning proton beam for both GATE and PHITS codes by using data from FLUKA simulation as a reference. The proton beam scanning system of the Indiana University Health Proton Therapy Center was modeled in FLUKA, and the geometry was subsequently and identically transferred to GATE and PHITS. Although the beam transport is managed by spot scanning system, the spot location is always set at the center of a water phantom of 600 × 600 × 300 mm3, which is placed after the treatment nozzle. The percentage depth dose (PDD) is computed along the central axis using 0.5 × 0.5 × 0.5 mm3 voxels in the water phantom. The PDDs and the proton ranges obtained with several computational parameters are then compared to those of FLUKA, and optimal parameters are determined from the accuracy of the proton range, suppressed dose deviation, and computational time minimization. Our results indicate that the optimized parameters are different from those for uniform scanning, suggesting that the gold standard for setting computational parameters for any proton therapy application cannot be determined consistently since the impact of setting parameters depends on the proton irradiation technique. We therefore conclude that customization parameters must be set with reference to the optimized parameters of the corresponding irradiation technique in order to render them useful for achieving artifact-free MC simulation for use in computational experiments and clinical treatments.

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

Collision-induced dissociation processes of protonated benzoic acid and related compounds: competitive generation of protonated carbon dioxide or protonated benzene.

PubMed

Xu, Sihang; Pavlov, Julius; Attygalle, Athula B

2017-04-01

Upon activation in the gas phase, protonated benzoic acid (m/z 123) undergoes fragmentation by several mechanisms. In addition to the predictable water loss followed by a CO loss, the m/z 123 ion more intriguingly eliminates a molecule of benzene to generate protonated carbon dioxide (H - O +  ═ C ≡ O, m/z 45), or a molecule of carbon dioxide to yield protonated benzene (m/z 79). Experimental evidence shows that the incipient proton ambulates during the fragmentation processes. For the CO 2 or benzene loss, protonated benzoic acid transfers the charge-imparting proton initially to the ortho position and then to the ipso position to generate a transient species which dissociates to form an ion-neutral complex between benzene and protonated CO 2 . The formation of the m/z 45 ion is not a phenomenon unique to benzoic acid: spectra from protonated isophthalic acid, terephthalic acid, trans-cinnamic acid and some aliphatic acids also displayed a peak for m/z 45. However, the m/z 45 peak is structurally diagnostic only for certain benzene polycarboxylic acids because the spectra of compounds with two carboxyl groups on adjacent ring carbons do not produce a peak at m/z 45. For the m/z 79 ion to be formed, an intramolecular reaction should take place in which protonated CO 2 within the ion-neutral complex acts as the attacking electrophile to transfer a proton to benzene. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Monitoring acute phase proteins in retrovirus infected cats undergoing feline interferon-ω therapy.

PubMed

Leal, R O; Gil, S; Sepúlveda, N; McGahie, D; Duarte, A; Niza, M M R E; Tavares, L

2014-01-01

Recombinant feline interferon-ω therapy is an immunomodulator currently used in the treatment of different retroviral diseases including feline immune deficiency virus and feline leukaemia virus. Although its mechanism of action remains unclear, this drug appears to potentiate the innate response. Acute phase proteins are one of the key components of innate immunity and studies describing their use as a monitoring tool for the immune system in animals undergoing interferon-ω therapy are lacking. This study aimed to determine whether interferon-ω therapy influences acute phase protein concentrations namely serum amyloid-A, α-1-glycoprotein and C-reactive protein. A single-arm study was performed using 16 cats, living in an animal shelter, naturally infected with retroviruses and subjected to the interferon-ω therapy licensed protocol. Samples were collected before (D0), during (D10 and D30) and after therapy (D65). Serum amyloid-A and C-reactive protein were measured by specific enzyme-linked immunosorbent assay kits and α-1-glycoprotein by single radial immunodiffusion. All the acute phase proteins significantly increased in cats undergoing interferon-ω therapy (D0/D65: P<0·05) CLINICAL SIGNIFICANCE: Acute phase proteins appear to be reasonable predictors of innate-immune stimulation and may be useful in the individual monitoring of naturally retroviral infected cats undergoing interferon-ω therapy. © 2013 British Small Animal Veterinary Association.

Proton beam therapy control system

DOEpatents

Baumann, Michael A [Riverside, CA; Beloussov, Alexandre V [Bernardino, CA; Bakir, Julide [Alta Loma, CA; Armon, Deganit [Redlands, CA; Olsen, Howard B [Colton, CA; Salem, Dana [Riverside, CA

2008-07-08

A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

Proton beam therapy control system

DOEpatents

Baumann, Michael A.; Beloussov, Alexandre V.; Bakir, Julide; Armon, Deganit; Olsen, Howard B.; Salem, Dana

2010-09-21

A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

Proton beam therapy control system

DOEpatents

Baumann, Michael A; Beloussov, Alexandre V; Bakir, Julide; Armon, Deganit; Olsen, Howard B; Salem, Dana

2013-06-25

A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

Proton beam therapy control system

DOEpatents

Baumann, Michael A; Beloussov, Alexandre V; Bakir, Julide; Armon, Deganit; Olsen, Howard B; Salem, Dana

2013-12-03

A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

Proton Radiography With Timepix Based Time Projection Chambers.

PubMed

Biegun, Aleksandra K; Visser, Jan; Klaver, Tom; Ghazanfari, Nafiseh; van Goethem, Marc-Jan; Koffeman, Els; van Beuzekom, Martin; Brandenburg, Sytze

2016-04-01

The development of a proton radiography system to improve the imaging of patients in proton beam therapy is described. The system comprises gridpix based time projection chambers, which are based on the Timepix chip designed by the Medipix collaboration, for tracking the protons. This type of detector was chosen to have minimal impact on the actual determination of the proton tracks by the tracking detectors. To determine the residual energy of the protons, a BaF 2 crystal with a photomultiplier tube is used. We present data taken in a feasibility experiment with phantoms that represent tissue equivalent materials found in the human body. The obtained experimental results show a good agreement with the performed simulations.

UK's first NHS high-energy proton beam facility.

PubMed

Shaw, Phil

2017-05-01

With the UK's first high-energy Proton Beam Therapy Centre set to open next year at Manchester's The Christie, young patients with head and neck tumours, cancers close to the skull or spine, or a variety of soft tissue tumours, and adults with cancers difficult to treat using 'conventional' photon-based radiotherapy will, for the first time, be able to receive NHS proton beam therapy (PBT) without having to travel overseas. HEJ editor, Jonathan Baillie, visited the site of The Christie's new £135 million PBT Centre to find out more about the design and construction of a facility which interserve construction director for the North-West, Phil Shaw, describes as one of the most complex and specialist he has worked on.

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-111: Development of Proton Dosimetry System Using Fiber-Optic Cerenkov Radiation Sensor Array

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

Son, J; Kim, M; Shin, D

2014-06-01

Purpose: We had developed and evaluated a new dosimetric system for proton therapy using array of fiber-optic Cerenkov radiation sensor (FOCRS) which can measure a percent depth dose (PDD) instantly. In this study, the Bragg peaks and spread out Bragg peak (SOBP) of the proton beams measured by FOCRS array were compared with those measured by an ion chamber. Methods and Method: We fabricated an optical fiber array of FOCRS in a handmade phantom which is composed of poly-methyl methacrylate (PMMA). There are 75 holes of 1mm diameter inside the phantom which is designed to be exposed in direction ofmore » beam when it is emerged in water phantom. The proton beam irradiation was carried out using IBA cyclotron PROTEUS 235 at national cancer center in Korea and a commercial data acquisition system was used to digitize the analog signal. Results: The measured Bragg peak and SOBP for the proton ranges of 7∼ 20 cm were well matched with the result from ion chamber. The comparison results show that the depth of proton beam ranges and the width of SOBP measured by array of FOCRS are comparable with the measurement from multi-layer ion chamber (MLIC) although there are some uncertainty in the measurement of FOCRS array for some specific beam ranges. Conclusion: The newly developed FOCRS array based dosimetric system for proton therapy can efficiently reduce the time and effort needed for proton beam range measurement compared to the conventional method and has the potential to be used for the proton pencil beam application.« less

The development and clinical use of a beam ON-LINE PET system mounted on a rotating gantry port in proton therapy.

PubMed

Nishio, Teiji; Miyatake, Aya; Ogino, Takashi; Nakagawa, Keiichi; Saijo, Nagahiro; Esumi, Hiroyasu

2010-01-01

To verify the usefulness of our developed beam ON-LINE positron emission tomography (PET) system mounted on a rotating gantry port (BOLPs-RGp) for dose-volume delivery-guided proton therapy (DGPT). In the proton treatment room at our facility, a BOLPs-RGp was constructed so that a planar PET apparatus could be mounted with its field of view covering the iso-center of the beam irradiation system. Activity measurements were performed in 48 patients with tumors of the head and neck, liver, lungs, prostate, and brain. The position and intensity of the activity were measured using the BOLPs-RGp during the 200 s immediately after the proton irradiation. The daily measured activity images acquired by the BOLPs-RGp showed the proton irradiation volume in each patient. Changes in the proton-irradiated volume were indicated by differences between a reference activity image (taken at the first treatment) and the daily activity-images. In the case of head-and-neck treatment, the activity distribution changed in the areas where partial tumor reduction was observed. In the case of liver treatment, it was observed that the washout effect in necrotic tumor cells was slower than in non-necrotic tumor cells. The BOLPs-RGp was developed for the DGPT. The accuracy of proton treatment was evaluated by measuring changes of daily measured activity. Information about the positron-emitting nuclei generated during proton irradiation can be used as a basis for ensuring the high accuracy of irradiation in proton treatment.

The Potential Benefit of Radiotherapy with Protons in Head and Neck Cancer with Respect to Normal Tissue Sparing: A Systematic Review of Literature

PubMed Central

Bijl, Hendrik P.; Schilstra, Cornelis; Pijls-Johannesma, Madelon; Langendijk, Johannes A.

2011-01-01

Purpose. Clinical studies concerning head and neck cancer patients treated with protons reporting on radiation-induced side effects are scarce. Therefore, we reviewed the literature regarding the potential benefits of protons compared with the currently used photons in terms of lower doses to normal tissue and the potential for fewer subsequent radiation-induced side effects, with the main focus on in silico planning comparative (ISPC) studies. Materials and Methods. A literature search was performed by two independent researchers on ISPC studies that included proton-based and photon-based irradiation techniques. Results. Initially, 877 papers were retrieved and 14 relevant and eligible ISPC studies were identified and included in this review. Four studies included paranasal sinus cancer cases, three included nasopharyngeal cancer cases, and seven included oropharyngeal, hypopharyngeal, and/or laryngeal cancer cases. Seven studies compared the most sophisticated photon and proton techniques: intensity-modulated photon therapy versus intensity-modulated proton therapy (IMPT). Four studies compared different proton techniques. All studies showed that protons had a lower normal tissue dose, while keeping similar or better target coverage. Two studies found that these lower doses theoretically translated into a significantly lower incidence of salivary dysfunction. Conclusion. The results of ISPC studies indicate that protons have the potential for a significantly lower normal tissue dose, while keeping similar or better target coverage. Scanned IMPT probably offers the most advantage and will allow for a substantially lower probability of radiation-induced side effects. The results of these ISPC studies should be confirmed in properly designed clinical trials. PMID:21349950

21 CFR 892.5050 - Medical charged-particle radiation therapy system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical charged-particle radiation therapy system...-particle radiation therapy system. (a) Identification. A medical charged-particle radiation therapy system is a device that produces by acceleration high energy charged particles (e.g., electrons and protons...

21 CFR 892.5050 - Medical charged-particle radiation therapy system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical charged-particle radiation therapy system...-particle radiation therapy system. (a) Identification. A medical charged-particle radiation therapy system is a device that produces by acceleration high energy charged particles (e.g., electrons and protons...

21 CFR 892.5050 - Medical charged-particle radiation therapy system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical charged-particle radiation therapy system...-particle radiation therapy system. (a) Identification. A medical charged-particle radiation therapy system is a device that produces by acceleration high energy charged particles (e.g., electrons and protons...

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

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.

TU-G-213-00: The International Electrotechnical Commission (IEC): What Is It and Why Should Medical Physicists Care?

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

NONE

The International Electrotechnical Commission (IEC) writes standards that manufacturers of electrical equipment must comply with. Medical electrical equipment, such as medical imaging, radiation therapy, and radiation dosimetry devices, fall under Technical Committee 62. Of particular interest to medical physicists are the standards developed within Subcommittees (SC) 62B, which addresses diagnostic radiological imaging equipment, and 62C, which addresses equipment for radiation therapy, nuclear medicine and dosimetry. For example, a Working Group of SC 62B is responsible for safety and quality assurance standards for CT scanners and a Working Group of SC 62C is responsible for standards that set requirements for dosimetricmore » safety and accuracy of linacs and proton accelerators. IEC standards thus have an impact on every aspect of a medical physicist’s job, including equipment testing, shielding design, room layout, and workflow. Consequently, it is imperative that US medical physicists know about existing standards, as well as have input on those under development or undergoing revision. The structure of the IEC and current standards development work will be described in detail. The presentation will explain how US medical physicists can learn about IEC standards and contribute to their development. Learning Objectives: Learn about the structure of the IEC and the influence that IEC standards have on the design of equipment for radiology and radiation therapy. Learn about the mechanisms by which the US participates in the development and revision of standards. Understand the specific requirements of several standards having direct relevance to diagnostic and radiation therapy physicists.« less

TU-G-213-01: IEC and US Committee Activities and Organizational Structure

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

Ibbott, G.

2015-06-15

The International Electrotechnical Commission (IEC) writes standards that manufacturers of electrical equipment must comply with. Medical electrical equipment, such as medical imaging, radiation therapy, and radiation dosimetry devices, fall under Technical Committee 62. Of particular interest to medical physicists are the standards developed within Subcommittees (SC) 62B, which addresses diagnostic radiological imaging equipment, and 62C, which addresses equipment for radiation therapy, nuclear medicine and dosimetry. For example, a Working Group of SC 62B is responsible for safety and quality assurance standards for CT scanners and a Working Group of SC 62C is responsible for standards that set requirements for dosimetricmore » safety and accuracy of linacs and proton accelerators. IEC standards thus have an impact on every aspect of a medical physicist’s job, including equipment testing, shielding design, room layout, and workflow. Consequently, it is imperative that US medical physicists know about existing standards, as well as have input on those under development or undergoing revision. The structure of the IEC and current standards development work will be described in detail. The presentation will explain how US medical physicists can learn about IEC standards and contribute to their development. Learning Objectives: Learn about the structure of the IEC and the influence that IEC standards have on the design of equipment for radiology and radiation therapy. Learn about the mechanisms by which the US participates in the development and revision of standards. Understand the specific requirements of several standards having direct relevance to diagnostic and radiation therapy physicists.« less

TU-G-213-03: IEC Subcommittee 62C (Equipment for Radiotherapy, Nuclear Medicine and Radiation Dosimetry): Recent and Active Projects

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

Culberson, W.

The International Electrotechnical Commission (IEC) writes standards that manufacturers of electrical equipment must comply with. Medical electrical equipment, such as medical imaging, radiation therapy, and radiation dosimetry devices, fall under Technical Committee 62. Of particular interest to medical physicists are the standards developed within Subcommittees (SC) 62B, which addresses diagnostic radiological imaging equipment, and 62C, which addresses equipment for radiation therapy, nuclear medicine and dosimetry. For example, a Working Group of SC 62B is responsible for safety and quality assurance standards for CT scanners and a Working Group of SC 62C is responsible for standards that set requirements for dosimetricmore » safety and accuracy of linacs and proton accelerators. IEC standards thus have an impact on every aspect of a medical physicist’s job, including equipment testing, shielding design, room layout, and workflow. Consequently, it is imperative that US medical physicists know about existing standards, as well as have input on those under development or undergoing revision. The structure of the IEC and current standards development work will be described in detail. The presentation will explain how US medical physicists can learn about IEC standards and contribute to their development. Learning Objectives: Learn about the structure of the IEC and the influence that IEC standards have on the design of equipment for radiology and radiation therapy. Learn about the mechanisms by which the US participates in the development and revision of standards. Understand the specific requirements of several standards having direct relevance to diagnostic and radiation therapy physicists.« less

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

Acute Toxicity and Quality of Life in Patients With Prostate Cancer Treated With Protons or Carbon Ions in a Prospective Randomized Phase II Study—The IPI Trial

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

Habl, Gregor; Department of Radiation Oncology, Technische Universität München, Munich; Uhl, Matthias

Purpose: The purpose of this study was to compare safety and feasibility of proton therapy with that of carbon ion therapy in hypofractionated raster-scanned irradiation of the prostate, in a prospective randomized phase 2 trial. Methods and Materials: In this trial, 92 patients with localized prostate cancer were enrolled. Patients were randomized to receive either proton therapy (arm A) or carbon ion therapy (arm B) and treated with a total dose of 66 Gy(relative biological effectiveness [RBE]) administered in 20 fractions (single dose of 3.3 Gy[RBE]). Patients were stratified by the use of antihormone therapy. Primary endpoint was the combined assessment ofmore » safety and feasibility. Secondary endpoints were specific toxicities, prostate-specific antigen progression-free survival (PFS), overall survival (OS), and quality of life (QoL). Results: Ninety-one patients completed therapy and have had a median follow-up of 22.3 months. Among acute genitourinary toxicities, grade 1 cystitis rates were 34.1% (39.1% in A; 28.9% in B) and 17.6% grade 2 (21.7% in A; 13.3% in B). Seven patients (8%) required urinary catheterization during treatment due to urinary retention, 5 of whom were in arm A. Regarding acute gastrointestinal toxicities, 2 patients treated with protons developed grade 3 rectal fistulas. Grade 1 radiation proctitis occurred in 12.1% (13.0% in A; 11.1% in B) and grade 2 in 5.5% (8.7% in A; 2.2% in B). No statistically significant differences in toxicity profiles between arms were found. Reduced QoL was evident mainly in fatigue, pain, and urinary symptoms during therapy and 6 weeks thereafter. All European Organization for Research and Treatment of Cancer QLQ-C30 and -PR25 scores improved during follow-up. Conclusions: Hypofractionated irradiation using either carbon ions or protons results in comparable acute toxicities and QoL parameters. We found that hypofractionated particle irradiation is feasible and may be safe. Due to the occurrence of gel in the rectal wall and the consecutive occurrence of 2 rectal fistulas, we stopped using the insertion of spacer gel. Longer follow-up is necessary for evaluation of PFS and OS. (Ion Prostate Irradiation (IPI); (NCT01641185); (ClinicalTrials.gov).)« less

Protonation-dependent conformational dynamics of the multidrug transporter EmrE

PubMed Central

Dastvan, Reza; Mishra, Smriti; Meiler, Jens; Mchaourab, Hassane S.

2016-01-01

The small multidrug transporter from Escherichia coli, EmrE, couples the energetically uphill extrusion of hydrophobic cations out of the cell to the transport of two protons down their electrochemical gradient. Although principal mechanistic elements of proton/substrate antiport have been described, the structural record is limited to the conformation of the substrate-bound state, which has been shown to undergo isoenergetic alternating access. A central but missing link in the structure/mechanism relationship is a description of the proton-bound state, which is an obligatory intermediate in the transport cycle. Here we report a systematic spin labeling and double electron electron resonance (DEER) study that uncovers the conformational changes of EmrE subsequent to protonation of critical acidic residues in the context of a global description of ligand-induced structural rearrangements. We find that protonation of E14 leads to extensive rotation and tilt of transmembrane helices 1–3 in conjunction with repacking of loops, conformational changes that alter the coordination of the bound substrate and modulate its access to the binding site from the lipid bilayer. The transport model that emerges from our data posits a proton-bound, but occluded, resting state. Substrate binding from the inner leaflet of the bilayer releases the protons and triggers alternating access between inward- and outward-facing conformations of the substrate-loaded transporter, thus enabling antiport without dissipation of the proton gradient. PMID:26787875

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

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

Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as wellmore » as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.« less

Decision support tools for proton therapy ePR: intelligent treatment planning navigator and radiation toxicity tool for evaluating of prostate cancer treatment

NASA Astrophysics Data System (ADS)

Le, Anh H.; Deshpande, Ruchi; Liu, Brent J.

2010-03-01

The electronic patient record (ePR) has been developed for prostate cancer patients treated with proton therapy. The ePR has functionality to accept digital input from patient data, perform outcome analysis and patient and physician profiling, provide clinical decision support and suggest courses of treatment, and distribute information across different platforms and health information systems. In previous years, we have presented the infrastructure of a medical imaging informatics based ePR for PT with functionality to accept digital patient information and distribute this information across geographical location using Internet protocol. In this paper, we present the ePR decision support tools which utilize the imaging processing tools and data collected in the ePR. The two decision support tools including the treatment plan navigator and radiation toxicity tool are presented to evaluate prostate cancer treatment to improve proton therapy operation and improve treatment outcomes analysis.

A Bayesian Approach for Measurements of Stray Neutrons at Proton Therapy Facilities: Quantifying Neutron Dose Uncertainty.

PubMed

Dommert, M; Reginatto, M; Zboril, M; Fiedler, F; Helmbrecht, S; Enghardt, W; Lutz, B

2017-11-28

Bonner sphere measurements are typically analyzed using unfolding codes. It is well known that it is difficult to get reliable estimates of uncertainties for standard unfolding procedures. An alternative approach is to analyze the data using Bayesian parameter estimation. This method provides reliable estimates of the uncertainties of neutron spectra leading to rigorous estimates of uncertainties of the dose. We extend previous Bayesian approaches and apply the method to stray neutrons in proton therapy environments by introducing a new parameterized model which describes the main features of the expected neutron spectra. The parameterization is based on information that is available from measurements and detailed Monte Carlo simulations. The validity of this approach has been validated with results of an experiment using Bonner spheres carried out at the experimental hall of the OncoRay proton therapy facility in Dresden. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Proton Electrostatic Analyzer.

DTIC Science & Technology

1983-02-01

Detector Assembly ......................................... 11 2.2 Analyzer (Energy Selector) Assembly............................ 12 2.3 Collimator...Spectrometer assembly ........................................ 13 2.2 Base plate .................................................. 14 - ~ 2.3 Detector ... sensitive vehicle systems. Space objects undergo differential charging due to variations in physical properties among their surface regions. The rate and

High gradient linac for proton therapy

NASA Astrophysics Data System (ADS)

Benedetti, S.; Grudiev, A.; Latina, A.

2017-04-01

Proposed for the first time almost 30 years ago, the research on radio frequency linacs for hadron therapy experienced a sparkling interest in the past decade. The different projects found a common ground on a relatively high rf operating frequency of 3 GHz, taking advantage of the availability of affordable and reliable commercial klystrons at this frequency. This article presents for the first time the design of a proton therapy linac, called TULIP all-linac, from the source up to 230 MeV. In the first part, we will review the rationale of linacs for hadron therapy. We then divided this paper in two main sections: first, we will discuss the rf design of the different accelerating structures that compose TULIP; second, we will present the beam dynamics design of the different linac sections.

Mitigation of Cancer Therapy Side-Effects with Light

NASA Astrophysics Data System (ADS)

Nair, Raj; Bensadoun, René-Jean

2016-10-01

'Light' from low level laser therapy, through a process called photobiomodulation (PBM), has been in existence in supportive care in cancer, in particular in the management of oral mucositis (OM) in patients undergoing chemotherapy, radiation therapy and haematopoietic stem cell transplantation. In this book the authors attempt to portray the current status of the supportive care interventions that are possible with PBM using low level laser therapy (LLLT) in patients undergoing cancer treatment for solid tumours, harmatological malignancies, and head and neck cancers.

Accelerating gradient improvement from hole-boring to light-sail stage using shape-tailored laser front

NASA Astrophysics Data System (ADS)

Wang, W. P.; Shen, B. F.; Xu, Z. Z.

2017-01-01

The accelerating gradient of a proton beam is a crucial factor for the stable radiation pressure acceleration, because quickly accelerating protons into the relativistic region may reduce the multidimensional instability grow to a certain extent. In this letter, a shape-tailored laser is designed to accelerate the protons in a controllable high accelerating gradient in theory. Finally, a proton beam in the gigaelectronvolt range with an energy spread of ˜2.4% is obtained in one-dimensional particle-in-cell simulations. With the future development of the high-intense laser, the ability to accelerate a high energy proton beam using a shape-tailored laser will be important for realistic proton applications, such as fast ignition for inertial confinement fusion, medical therapy, and proton imaging.

Deprotonation of hydrogen bonded Schiff bases by three strong nitrogen bases

NASA Astrophysics Data System (ADS)

Schilf, Wojciech; Cmoch, Piotr; Szady-Chełmieniecka, Anna; Grech, Eugeniusz

2009-03-01

Three Schiff bases obtained from substituted salicylaldehydes and 2-hydroxy-1-naphthaldehyde and aliphatic amines were investigated in terms of possible withdrawal of tautomeric proton from intramolecular hydrogen bridge. Three strong nitrogen bases: 1,8-bis(dimethylamino)naphtalene (DMAN), 1,1,3,3-tetramethylguanidine (TMG) and 1,8-bis(tetramethylguanidino)naphthalene (TMGN) were used as deprotonating agents in acetonitrile solution at room temperature. In the specified conditions it was found that only in the case of 5-nitrosalicylaldehyde and isopropyl amine derivative this process could be performed using TMG and TMGN as a base. The other derivatives, where bridged proton is shifted to oxygen or nitrogen atom, do not undergo such reaction. The deprotonation process was monitored by nitrogen and proton NMR measurements.

Tevatron Top-Quark Combinations and World Top-Quark Mass Combination

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

Peters, Reinhild Yvonne

2014-11-04

Almost 20 years after its discovery, the top quark is still an interesting particle, undergoing precise investigation of its properties. For many years, the Tevatron proton antiproton collider at Fermilab was the only place to study top quarks in detail, while with the recent start of the LHC proton proton collider a top quark factory has opened. An important ingredient for the full understanding of the top quark is the combination of measurements from the individual experiments. In particular, the Tevaton combinations of single top-quark cross sections, the ttbar production cross section, the W helicity in top-quark decays as wellmore » as the Tevatron and the world combination of the top-quark mass are discussed.« less

Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

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

Sethi, Roshan V.; Giantsoudi, Drosoula; Raiford, Michael

2014-03-01

Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine themore » LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.« less

An experimental demonstration of a new type of proton computed tomography using a novel silicon tracking detector.

PubMed

Taylor, J T; Poludniowski, G; Price, T; Waltham, C; Allport, P P; Casse, G L; Esposito, M; Evans, P M; Green, S; Manger, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Symons, J; Allinson, N M

2016-11-01

Radiography and tomography using proton beams promise benefit to image guidance and treatment planning for proton therapy. A novel proton tracking detector is described and experimental demonstrations at a therapy facility are reported. A new type of proton CT reconstructing relative "scattering power" rather than "stopping power" is also demonstrated. Notably, this new type of imaging does not require the measurement of the residual energies of the protons. A large area, silicon microstrip tracker with high spatial and temporal resolution has been developed by the Proton Radiotherapy Verification and Dosimetry Applications consortium and commissioned using beams of protons at iThemba LABS, Medical Radiation Department, South Africa. The tracker comprises twelve planes of silicon developed using technology from high energy physics with each plane having an active area of ∼10 × 10 cm segmented into 2048 microstrips. The tracker is organized into four separate units each containing three detectors at 60° to one another creating an x-u-v coordinate system. Pairs of tracking units are used to reconstruct vertices for protons entering and exiting a phantom containing tissue equivalent inserts. By measuring the position and direction of each proton before and after the phantom, the nonlinear path for each proton through an object can be reconstructed. Experimental results are reported for tracking the path of protons with initial energies of 125 and 191 MeV. A spherical phantom of 75 mm diameter was imaged by positioning it between the entrance and exit detectors of the tracker. Positions and directions of individual protons were used to create angular distributions and 2D fluence maps of the beam. These results were acquired for 36 equally spaced projections spanning 180°, allowing, for the first time, an experimental CT image based upon the relative scattering power of protons to be reconstructed. Successful tracking of protons through a thick target (phantom) has demonstrated that the tracker discussed in this paper can provide the precise directional information needed to perform proton radiography and tomography. When synchronized with a range telescope, this could enable the reconstruction of proton CT images of stopping power. Furthermore, by measuring the deflection of many protons through a phantom, it was demonstrated that it is possible to reconstruct a new kind of CT image (scattering power) based upon this tracking information alone.

Development of a Multileaf Collimator for Proton Radiotherapy

DTIC Science & Technology

2010-06-01

generated and compared to the dosimetry derived from radiochromic media. TLDS may be inserted into the phantom to further confirm the technique. Finally...of dosimetry systems for scanned beams: (FY 2006-2009). We are investigating dosimetry systems for use with scanned beams and will either purchase a...group Research in Monte Carlo Simulations and Dosimetry Studies of Proton Therapy Rulon Mayer, PhD Energetic protons used to damage tumors

[Diseases linked to Helicobacter pylori infection].

PubMed

Gisbert, Javier P

2014-09-01

Below is a summary of the main conclusions that came from reports presented at this year's Digestive Disease Week (2014) relating to Helicobacter pylori infection. Despite the undeniable decline of the infection's frequency, in the near future, developed countries--or at least some sub-populations--will continue to have a significant prevalence of the infection. Clarithromycin, metronidazole and quinolone resistance rates are considerably high in most countries and these rates are on the rise. The eradication of H. pylori improves symptoms of functional dyspepsia, although only in a minority of patients; adding antidepressants to eradication therapy could improve long-term response. In patients who were admitted with gastrointestinal bleeding from peptic ulcers, it is necessary to thoroughly study the presence of H. pylori infection and administer eradication therapy as early as possible. Eradication of H. pylori in patients undergoing endoscopic resection of early-stage gastric cancer reduces incidence of metachronous tumors. We have some diagnostic innovations, such as carrying out various techniques--a rapid urease test, culture or PCR--based on gastric samples obtained by scraping the mucosa. The effectiveness of conventional triple therapy is clearly insufficient and continues to decline. The superiority of sequential therapy over conventional triple therapies has not been definitively established. Concomitant therapy is simpler and more effective than sequential therapy. Optimized concomitant therapy (with high doses of proton-pump inhibitors [PPI] and over 14 days) is highly effective, more so than standard concomitant therapy. For patients who are allergic to penicillin, 2 treatment options were essentially described: PPI-clarithromycin-metronidazole (clarithromycin-sensitive strains) and quadruple therapy with bismuth (when the bacterial sensitivity is unknown). If conventional triple therapy fails, second-line therapy with levofloxacin is effective and is also easier and better tolerated than quadruple therapy with bismuth. Triple therapy with levofloxacin is also a promising alternative if sequential or concomitant therapy fails. New-generation quinolones, such as moxifloxacin, could be useful as part of rescue eradication therapy. Even after 3 eradication therapies have failed, a fourth empirical rescue therapy (with rifabutin) could be effective. The eradication of H. pylori can finally be obtained in the vast majority of patients by using a rescue strategy of up to 4 consecutive empirical therapies, without conducting bacterial cultures. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

An analytical model of leakage neutron equivalent dose for passively-scattered proton radiotherapy and validation with measurements.

PubMed

Schneider, Christopher; Newhauser, Wayne; Farah, Jad

2015-05-18

Exposure to stray neutrons increases the risk of second cancer development after proton therapy. Previously reported analytical models of this exposure were difficult to configure and had not been investigated below 100 MeV proton energy. The purposes of this study were to test an analytical model of neutron equivalent dose per therapeutic absorbed dose  at 75 MeV and to improve the model by reducing the number of configuration parameters and making it continuous in proton energy from 100 to 250 MeV. To develop the analytical model, we used previously published H/D values in water from Monte Carlo simulations of a general-purpose beamline for proton energies from 100 to 250 MeV. We also configured and tested the model on in-air neutron equivalent doses measured for a 75 MeV ocular beamline. Predicted H/D values from the analytical model and Monte Carlo agreed well from 100 to 250 MeV (10% average difference). Predicted H/D values from the analytical model also agreed well with measurements at 75 MeV (15% average difference). The results indicate that analytical models can give fast, reliable calculations of neutron exposure after proton therapy. This ability is absent in treatment planning systems but vital to second cancer risk estimation.

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

Hata, Masaharu; Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki; Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa

Purpose: To investigate the safety and efficacy of proton beam therapy for aged patients with hepatocellular carcinoma (HCC). Methods and Materials: Twenty-one patients aged {>=}80 years with HCC underwent proton beam therapy. At the time of irradiation, patient age ranged from 80 to 85 years (median, 81 years). Hepatic tumors were solitary in 17 patients and multiple in 4. Tumor size ranged from 10 to 135 mm (median, 40 mm) in maximum diameter. Ten, 5, and 6 patients received proton beam irradiation with total doses of 60 Gy in 10 fractions, 66 Gy in 22 fractions, and 70 Gy inmore » 35 fractions, respectively, according to tumor location. Results: All irradiated tumors were controlled during the follow-up period of 6-49 months (median, 16 months). Five patients showed new hepatic tumors outside the irradiated volume, 2-13 months after treatment, and 1 of them also had lung metastasis. The local progression-free and disease-free rates were 100% and 72% at 3 years, respectively. Of 21 patients, 7 died 6-49 months after treatment; 2 patients each died of trauma and old age, and 1 patient each died of HCC, pneumonia, and arrhythmia. The 3-year overall, cause-specific, and disease-free survival rates were 62%, 88%, and 51%, respectively. No therapy-related toxicity of Grade {>=} 3 but thrombocytopenia in 2 patients was observed. Conclusions: Proton beam therapy seems to be tolerable, effective, and safe for aged patients with HCC. It may contribute to prolonged survival due to tumor control.« less

Startup of the Kling Center for Proton Therapy

NASA Astrophysics Data System (ADS)

Bloch, C.; Hill, P. M.; Chen, K. L.; Saito, A.; Klein, E. E.

2013-04-01

In November of 2011 Mevion Medical Systems (formerly Still River Systems) delivered the Mevion S250 proton therapy system accelerator to the Kling Center for Proton Therapy at the Siteman Cancer Center in Saint Louis. The Mevion system is unique, with an in-room gantry-mounted superconducting synchrocyclotron. This is the first true single-room proton therapy system and it has a greatly reduced size as well as cost. A month after its arrival, the installation was complete and the superconducting magnet was ramped up to full current (˜2000 amperes). In March of 2012, full energy beam (250 MeV) was extracted and radiation surveys were performed to verify the shielding. Once that was shown to be sufficient, Mevion began fine-tuning the system to provide a highly isocentric beam from the 50 ton system. In June of 2012 the field-shaping system (energy degraders, contoured scatterers and range modulators) were installed and measurements of the clinical beam properties commenced. Monte Carlo simulations (MCNPX) have been performed for the system and validated with beam measurements done at the factory. These simulations have been used for a preliminary commissioning of our treatment planning system. Additionally, predictions of the neutron background have been made and validated with factory measurements. Final commissioning of the treatment planning system and verification of the neutron background will be accomplished with measurements made later in 2012. Based on current progress, patient treatments are scheduled to begin in late 2012. Beam and radiation background data will be presented.

Prophylactic use of bevacizumab to avoid anterior segment neovascularization following proton therapy for uveal melanoma.

PubMed

Mantel, Irmela; Schalenbourg, Ann; Bergin, Ciara; Petrovic, Aleksandra; Weber, Damien C; Zografos, Leonidas

2014-10-01

To investigate whether the prophylactic use of bevacizumab reduces the rate of rubeosis after proton therapy for uveal melanoma and improves the possibility to treat ischemic, reapplicated retina with laser photocoagulation. Comparative retrospective case series. Uveal melanoma patients with ischemic retinal detachment and treated with proton therapy were included in this institutional study. Twenty-four eyes received prophylactic intravitreal bevacizumab injections and were compared with a control group of 44 eyes without bevacizumab treatment. Bevacizumab injections were performed at the time of tantalum clip insertion and were repeated every 2 months during 6 months, and every 3 months thereafter. Ultra-widefield angiography allowed determination of the extent of retinal ischemia, which was treated with laser photocoagulation after retinal reapplication. Main outcome measures were the time to rubeosis, the time to retinal reattachment, and the time to laser photocoagulation of ischemic retina. Baseline characteristics were balanced between the groups, except for thicker tumors and larger retinal detachments in the bevacizumab group, potentially to the disadvantage of the study group. Nevertheless, bevacizumab prophylaxis significantly reduced the rate of iris rubeosis from 36% to 4% (log-rank test P = .02) and tended to shorten the time to retinal reapplication until laser photocoagulation of the nonperfusion areas could be performed. Prophylactic intravitreal bevacizumab in patients treated with proton therapy for uveal melanoma with ischemic retinal detachment prevented anterior segment neovascularization, until laser photocoagulation to the reapplied retina could be performed. Copyright © 2014 Elsevier Inc. All rights reserved.

Range assessment in particle therapy based on prompt γ-ray timing measurements

NASA Astrophysics Data System (ADS)

Golnik, Christian; Hueso-González, Fernando; Müller, Andreas; Dendooven, Peter; Enghardt, Wolfgang; Fiedler, Fine; Kormoll, Thomas; Roemer, Katja; Petzoldt, Johannes; Wagner, Andreas; Pausch, Guntram

2014-09-01

Proton and ion beams open up new vistas for the curative treatment of tumors, but adequate technologies for monitoring the compliance of dose delivery with treatment plans in real time are still missing. Range assessment, meaning the monitoring of therapy-particle ranges in tissue during dose delivery (treatment), is a continuous challenge considered a key for tapping the full potential of particle therapies. In this context the paper introduces an unconventional concept of range assessment by prompt-gamma timing (PGT), which is based on an elementary physical effect not considered so far: therapy particles penetrating tissue move very fast, but still need a finite transit time—about 1-2 ns in case of protons with a 5-20 cm range—from entering the patient’s body until stopping in the target volume. The transit time increases with the particle range. This causes measurable effects in PGT spectra, usable for range verification. The concept was verified by proton irradiation experiments at the AGOR cyclotron, KVI-CART, University of Groningen. Based on the presented kinematical relations, we describe model calculations that very precisely reproduce the experimental results. As the clinical treatment conditions entail measurement constraints (e.g. limited treatment time), we propose a setup, based on clinical irradiation conditions, capable of determining proton range deviations within a few seconds of irradiation, thus allowing for a fast safety survey. Range variations of 2 mm are expected to be clearly detectable.

SU-F-T-154: An Evaluation and Quantification of Secondary Neutron Radiation Dose Due to Double Scatter and Pencil Beam Scanning Proton Therapy

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

Glick, A; Diffenderfer, E

2016-06-15

Proton radiation therapy can deliver high radiation doses to tumors while sparing normal tissue. However, protons yield secondary neutron and gamma radiation that is difficult to detect, small in comparison to the prescribed dose, and not accounted for in most treatment planning systems. The risk for secondary malignancies after proton therapy may be dependent on the quality of this dose. Consequently, there is interest in characterizing the secondary radiation. Previously, we used the dual ionization chamber method to measure the separate absorbed dose from gamma-rays and neutrons secondary to the proton beam1, relying on characterization of ionization chamber response inmore » the unknown neutron spectrum from Monte Carlo simulation. We developed a procedure to use Shieldwerx activation foils, with neutron activation energies ranging from 0.025 eV to 13.5 MeV, to measure the neutron energy spectrum from double scattering (DS) and pencil beam scanning (PBS) protons outside of the treatment volume in a water tank. The activated foils are transferred to a NaI well chamber for gamma-ray spectroscopy and activity measurement. Since PBS treats in layers, the switching time between layers is used to correct for the decay of the activated foils and the relative dose per layer is assumed to be proportional to the neutron fluence per layer. MATLAB code was developed to incorporate the layer delivery and switching time into a calculation of foil activity, which is then used to determine the neutron energy fluence from tabulated foil activation energy thresholds.1. Diffenderfer et. al., Med. Phys., 38(11) 2011.« less

Results From the Imaging and Radiation Oncology Core Houston's Anthropomorphic Phantoms Used for Proton Therapy Clinical Trial Credentialing

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

Taylor, Paige A., E-mail: pataylor@mdanderson.org; Kry, Stephen F.; Alvarez, Paola

Purpose: The purpose of this study was to summarize the findings of anthropomorphic proton phantom irradiations analyzed by the Imaging and Radiation Oncology Core Houston QA Center (IROC Houston). Methods and Materials: A total of 103 phantoms were irradiated by proton therapy centers participating in clinical trials. The anthropomorphic phantoms simulated heterogeneous anatomy of a head, liver, lung, prostate, and spine. Treatment plans included those for scattered, uniform scanning, and pencil beam scanning beam delivery modalities using 5 different treatment planning systems. For every phantom irradiation, point doses and planar doses were measured using thermoluminescent dosimeters (TLD) and film, respectively. Differencesmore » between measured and planned doses were studied as a function of phantom, beam delivery modality, motion, repeat attempt, treatment planning system, and date of irradiation. Results: The phantom pass rate (overall, 79%) was high for simple phantoms and lower for phantoms that introduced higher levels of difficulty, such as motion, multiple targets, or increased heterogeneity. All treatment planning systems overestimated dose to the target, compared to TLD measurements. Errors in range calculation resulted in several failed phantoms. There was no correlation between treatment planning system and pass rate. The pass rates for each individual phantom are not improving over time, but when individual institutions received feedback about failed phantom irradiations, pass rates did improve. Conclusions: The proton phantom pass rates are not as high as desired and emphasize potential deficiencies in proton therapy planning and/or delivery. There are many areas for improvement with the proton phantom irradiations, such as treatment planning system dose agreement, range calculations, accounting for motion, and irradiation of multiple targets.« less

[1,5]-Anion relay via intramolecular proton transfer to generate 3,3-bis(silyl) allyloxy lithium: a useful scaffold for syn-addition to aldehydes and ketones.

PubMed

Lin, Xinglong; Ye, Xincui; Sun, Xianwei; Zhang, Yuebao; Gao, Lu; Song, Zhenlei

2014-02-21

A [1,5]-anion relay has been achieved in 3,3-bis(silyl) benzyl enol ether. Deprotonation at the sterically more accessible benzyl position triggers an intramolecular proton transfer to generate the thermodynamically more stable 3,3-bis(silyl) allyloxy lithium. This endo-oriented allyl anion is stable at -78 °C and undergoes diastereoselective syn-addition at the γ-position with aldehydes and ketones to give monobenzyl-substituted 1,2-diols.

Experimental and Theoretical Studies on Gas-Phase Fragmentation Reactions of Protonated Methyl Benzoate: Concomitant Neutral Eliminations of Benzene, Carbon Dioxide, and Methanol

NASA Astrophysics Data System (ADS)

Xia, Hanxue; Zhang, Yong; Attygalle, Athula B.

2018-06-01

Protonated methyl benzoate, upon activation, fragments by three distinct pathways. The m/z 137 ion for the protonated species generated by helium-plasma ionization (HePI) was mass-selected and subjected to collisional activation. In one fragmentation pathway, the protonated molecule generated a product ion of m/z 59 by eliminating a molecule of benzene (Pathway I). The m/z 59 ion (generally recognized as the methoxycarbonyl cation) produced in this way, then formed a methyl carbenium ion in situ by decarboxylation, which in turn evoked an electrophilic aromatic addition reaction on the benzene ring by a termolecular process to generate the toluenium cation (Pathway II). Moreover, protonated methyl benzoate undergoes also a methanol loss (Pathway III). However, it is not a simple removal of a methanol molecule after a protonation on the methoxy group. The incipient proton migrates to the ring and randomizes to a certain degree before a subsequent transfer of one of the ring protons to the alkoxy group for the concomitant methanol elimination. The spectrum recorded from deuteronated methyl benzoate showed two peaks at m/z 105 and 106 for the benzoyl cation at a ratio of 2:1, confirming the charge-imparting proton is mobile. However, the proton transfer from the benzenium intermediate to the methoxy group for the methanol loss occurs before achieving a complete state of scrambling. [Figure not available: see fulltext.

Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

PubMed

Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

2014-11-24

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Assessing the Clinical Impact of Approximations in Analytical Dose Calculations for Proton Therapy

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

Schuemann, Jan, E-mail: jschuemann@mgh.harvard.edu; Giantsoudi, Drosoula; Grassberger, Clemens

2015-08-01

Purpose: To assess the impact of approximations in current analytical dose calculation methods (ADCs) on tumor control probability (TCP) in proton therapy. Methods: Dose distributions planned with ADC were compared with delivered dose distributions as determined by Monte Carlo simulations. A total of 50 patients were investigated in this analysis with 10 patients per site for 5 treatment sites (head and neck, lung, breast, prostate, liver). Differences were evaluated using dosimetric indices based on a dose-volume histogram analysis, a γ-index analysis, and estimations of TCP. Results: We found that ADC overestimated the target doses on average by 1% to 2%more » for all patients considered. The mean dose, D95, D50, and D02 (the dose value covering 95%, 50% and 2% of the target volume, respectively) were predicted within 5% of the delivered dose. The γ-index passing rate for target volumes was above 96% for a 3%/3 mm criterion. Differences in TCP were up to 2%, 2.5%, 6%, 6.5%, and 11% for liver and breast, prostate, head and neck, and lung patients, respectively. Differences in normal tissue complication probabilities for bladder and anterior rectum of prostate patients were less than 3%. Conclusion: Our results indicate that current dose calculation algorithms lead to underdosage of the target by as much as 5%, resulting in differences in TCP of up to 11%. To ensure full target coverage, advanced dose calculation methods like Monte Carlo simulations may be necessary in proton therapy. Monte Carlo simulations may also be required to avoid biases resulting from systematic discrepancies in calculated dose distributions for clinical trials comparing proton therapy with conventional radiation therapy.« less

Spot-scanning proton therapy for malignant soft tissue tumors in childhood: First experiences at the Paul Scherrer Institute

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

Timmermann, Beate; Schuck, Andreas; Niggli, Felix

2007-02-01

Purpose: Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. Methods and Materials: Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III inmore » 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). Results: After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. Conclusions: Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed.« less

SU-E-T-396: Dosimetric Accuracy of Proton Therapy for Patients with Metal Implants in CT Scans Using Metal Deletion Technique (MDT) Artifacts Reduction

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

Li, X; Kantor, M; Zhu, X

2014-06-01

Purpose: To evaluate the dosimetric accuracy for proton therapy patients with metal implants in CT using metal deletion technique (MDT) artifacts reduction. Methods: Proton dose accuracies under CT metal artifacts were first evaluated using a water phantom with cylindrical inserts of different materials (titanium and steel). Ranges and dose profiles along different beam angles were calculated using treatment planning system (Eclipse version 8.9) on uncorrected CT, MDT CT, and manually-corrected CT, where true Hounsfield units (water) were assigned to the streak artifacts. In patient studies, the treatment plans were developed on manually-corrected CTs, then recalculated on MDT and uncorrected CTs.more » DVH indices were compared between the dose distributions on all the CTs. Results: For water phantom study with 1/2 inch titanium insert, the proton range differences estimated by MDT CT were with 1% for all beam angles, while the range error can be up to 2.6% for uncorrected CT. For the study with 1 inch stainless steel insert, the maximum range error calculated by MDT CT was 1.09% among all the beam angles compared with maximum range error with 4.7% for uncorrected CT. The dose profiles calculated on MDT CTs for both titanium and steel inserts showed very good agreements with the ones calculated on manually-corrected CTs, while large dose discrepancies calculated using uncorrected CTs were observed in the distal end region of the proton beam. The patient study showed similar dose distribution and DVHs for organs near the metal artifacts recalculated on MDT CT compared with the ones calculated on manually-corrected CT, while the differences between uncorrected and corrected CTs were much pronounced. Conclusion: In proton therapy, large dose error could occur due to metal artifact. The MDT CT can be used for proton dose calculation to achieve similar dose accuracy as the current clinical practice using manual correction.« 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-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

SU-E-T-622: Planning Technique for Passively-Scattered Involved-Node Proton Therapy of Mediastinal Lymphoma with Consideration of Cardiac Motion

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

Flampouri, S; Li, Z; Hoppe, B

2015-06-15

Purpose: To develop a treatment planning method for passively-scattered involved-node proton therapy of mediastinal lymphoma robust to breathing and cardiac motions. Methods: Beam-specific planning treatment volumes (bsPTV) are calculated for each proton field to incorporate pertinent uncertainties. Geometric margins are added laterally to each beam while margins for range uncertainty due to setup errors, breathing, and calibration curve uncertainties are added along each beam. The calculation of breathing motion and deformation effects on proton range includes all 4DCT phases. The anisotropic water equivalent margins are translated to distances on average 4DCT. Treatment plans are designed so each beam adequately coversmore » the corresponding bsPTV. For targets close to the heart, cardiac motion effects on dosemaps are estimated by using a library of anonymous ECG-gated cardiac CTs (cCT). The cCT, originally contrast-enhanced, are partially overridden to allow meaningful proton dose calculations. Targets similar to the treatment targets are drawn on one or more cCT sets matching the anatomy of the patient. Plans based on the average cCT are calculated on individual phases, then deformed to the average and accumulated. When clinically significant dose discrepancies occur between planned and accumulated doses, the patient plan is modified to reduce the cardiac motion effects. Results: We found that bsPTVs as planning targets create dose distributions similar to the conventional proton planning distributions, while they are a valuable tool for visualization of the uncertainties. For large targets with variability in motion and depth, integral dose was reduced because of the anisotropic margins. In most cases, heart motion has a clinically insignificant effect on target coverage. Conclusion: A treatment planning method was developed and used for proton therapy of mediastinal lymphoma. The technique incorporates bsPTVs compensating for all common sources of uncertainties and estimation of the effects of cardiac motion not commonly performed.« less

Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival

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

Eaton, Bree R.; Esiashvili, Natia; Kim, Sungjin

Purpose: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. Methods and Materials: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. Results: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection,more » craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). Conclusions: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.« less

Neutrons in active proton therapy: Parameterization of dose and dose equivalent.

PubMed

Schneider, Uwe; Hälg, Roger A; Lomax, Tony

2017-06-01

One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160MeV or 177MeV instead of 138MeV. For the neutron dose equivalent the increase is 8% and 57%. The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy. Copyright © 2016. Published by Elsevier GmbH.

Proton Radiation Therapy in the Hospital Environment: Conception, Development, and Operation of the Initial Hospital-Based Facility

NASA Astrophysics Data System (ADS)

Slater, James M.; Slater, Jerry D.; Wroe, Andrew J.

The world's first hospital-based proton treatment center opened at Loma Linda University Medical Center in 1990, following two decades of development. Patients' needs were the driving force behind its conception, development, and execution; the primary needs were delivery of effective conformal doses of ionizing radiation and avoidance of normal tissue to the maximum extent possible. The facility includes a proton synchrotron and delivery system developed in collaboration with physicists and engineers at Fermi National Accelerator Laboratory and from other high-energy-physics laboratories worldwide. The system, operated and maintained by Loma Linda personnel, was designed to be safe, reliable, flexible in utilization, efficient in use, and upgradeable to meet demands of changing patient needs and advances in technology. Since the facility opened, nearly 14,000 adults and children have been treated for a wide range of cancers and other diseases. Ongoing research is expanding the applications of proton therapy, while reducing costs.

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.

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.

Single-energy intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

2015-09-01

In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described. The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods. It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan. When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

Single-energy intensity modulated proton therapy.

PubMed

Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

2015-10-07

In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described.The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods.It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan.When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

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.

Comparing exercise responses to aerobic plus resistance training between postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy women.

PubMed

Paulo, Thais R S de; Winters-Stone, Kerri M; Viezel, Juliana; Rossi, Fabricio E; Aro, Bruna L; Trindade, Ana Carolina A C; Codogno, Jamile S; Freitas Junior, Ismael F

2018-04-12

The aim of this study was to explore whether postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy differ from healthy postmenopausal women in their response to the same aerobic + resistance training. The participants were separated into two groups: postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy for an average of 20 months (18 women) and healthy postmenopausal women (24 women). We assessed aerobic capacity (predicted maximum oxygen uptake (VO 2 max) and maximum running velocity test (Vmax)) through a walking test, upper and lower body muscle strength using an estimated one-repetition maximum test, and body composition by dual-energy X-ray absorptiometry at baseline and at three, six, and nine months, respectively. The exercise program was performed three times/week over nine months and consisted of 40 min of machine-based strength training (seated cable row, bench press, leg extension, leg press, and leg curl, as well as bridge, abdominal, and standard plank exercises) followed by 30 min of treadmill walking. Analysis of variance (ANOVA) with repeated measures was used to compare the groups over time. Postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy postmenopausal women presented similar improvements in estimated lower body strength, predicted VO 2max and V max , and body fat mass. For maximal upper body strength, there was a significant group x time interaction after six months of training (p = 0.01). The healthy postmenopausal women presented a significant increase in upper body strength after six months, while postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy demonstrated an improvement only at nine months of training. The breast cancer survivors undergoing aromatase inhibitor therapy presented increased lean mass while healthy postmenopausal women maintained values over time (Breast cancer: 33.7 ± 3.9(Pre) vs. 34.1 ± 3.4 kg (Post) and healthy women: 36.4 ± 5.1 (Pre) vs. 36.4 ± 5.0 kg (Post), p = 0.004). Our findings suggest that postmenopausal women undergoing aromatase inhibitor therapy for breast cancer demonstrated adaptations and similar trainability to the same regimen of resistance + aerobic training as healthy postmenopausal women. Implications for Rehabilitation Combined exercise program (aerobic plus resistance) is an important non-pharmacological strategies to improve strength, aerobic capacity, and body composition in breast cancer survivors undergoing aromatase inhibitor therapy. Furthermore, it is important to highlight that the time of intervention seems to influence the upper body strength response in this population. This study showed that trainers and other specialists do not need to modify the prescription of exercise related to healthy women, since the combined exercise program induced similar benefits in strength, aerobic capacity, and body composition in postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy postmenopausal women.

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

Off-axis dose equivalent due to secondary neutrons from uniform scanning proton beams during proton radiotherapy

NASA Astrophysics Data System (ADS)

Islam, M. R.; Collums, T. L.; Zheng, Y.; Monson, J.; Benton, E. R.

2013-11-01

The production of secondary neutrons is an undesirable byproduct of proton therapy and it is important to quantify the contribution from secondary neutrons to patient dose received outside the treatment volume. The purpose of this study is to investigate the off-axis dose equivalent from secondary neutrons experimentally using CR-39 plastic nuclear track detectors (PNTD) at ProCure Proton Therapy Center, Oklahoma City, OK. In this experiment, we placed several layers of CR-39 PNTD laterally outside the treatment volume inside a phantom and in air at various depths and angles with respect to the primary beam axis. Three different proton beams with max energies of 78, 162 and 226 MeV and 4 cm modulation width, a 5 cm diameter brass aperture, and a small snout located 38 cm from isocenter were used for the entire experiment. Monte Carlo simulations were also performed based on the experimental setup using a simplified snout configuration and the FLUKA Monte Carlo radiation transport code. The measured ratio of secondary neutron dose equivalent to therapeutic primary proton dose (H/D) ranged from 0.3 ± 0.08 mSv Gy-1 for 78 MeV proton beam to 37.4 ± 2.42 mSv Gy-1 for 226 MeV proton beam. Both experiment and simulation showed a similar decreasing trend in dose equivalent with distance to the central axis and the magnitude varied by a factor of about 2 in most locations. H/D was found to increase as the energy of the primary proton beam increased and higher H/D was observed at 135° compared to 45° and 90°. The overall higher H/D in air indicates the predominance of external neutrons produced in the nozzle rather than inside the body.

Concept of proton radiography using energy resolved dose measurement.

PubMed

Bentefour, El H; Schnuerer, Roland; Lu, Hsiao-Ming

2016-08-21

Energy resolved dosimetry offers a potential path to single detector based proton imaging using scanned proton beams. This is because energy resolved dose functions encrypt the radiological depth at which the measurements are made. When a set of predetermined proton beams 'proton imaging field' are used to deliver a well determined dose distribution in a specific volume, then, at any given depth x of this volume, the behavior of the dose against the energies of the proton imaging field is unique and characterizes the depth x. This concept applies directly to proton therapy scanning delivery methods (pencil beam scanning and uniform scanning) and it can be extended to the proton therapy passive delivery methods (single and double scattering) if the delivery of the irradiation is time-controlled with a known time-energy relationship. To derive the water equivalent path length (WEPL) from the energy resolved dose measurement, one may proceed in two different ways. A first method is by matching the measured energy resolved dose function to a pre-established calibration database of the behavior of the energy resolved dose in water, measured over the entire range of radiological depths with at least 1 mm spatial resolution. This calibration database can also be made specific to the patient if computed using the patient x-CT data. A second method to determine the WEPL is by using the empirical relationships between the WEPL and the integral dose or the depth at 80% of the proximal fall off of the energy resolved dose functions in water. In this note, we establish the evidence of the fundamental relationship between the energy resolved dose and the WEPL at the depth of the measurement. Then, we illustrate this relationship with experimental data and discuss its imaging dynamic range for 230 MeV protons.

[Helicobacter pylori-related diseases].

PubMed

Gisbert, Javier P

2013-10-01

This article summarizes the main conclusions drawn from the presentations on Helicobacter pylori at Digestive Disease Week 2013. Knowledge of this infection among the general population continues to be extremely limited. H. pylori is the main cause of "aging" of the human stomach. In developed countries, the prevalence of H. pylori infection has decreased but continues to be considerable. In most countries, clarithromycin and metronidazole resistance rates are markedly high. H. pylori eradication improves the symptoms of functional dyspepsia, but only in a minority of patients. The frequency of idiopathic peptic ulcers seems to be rising and their prognosis is worse. Most patients with gastric cancer have, or have had, prior H. pylori infection. The risk of developing preneoplastic lesions depends on the type (strain) of the microorganism. To prevent the development of gastric cancer, eradication therapy should be administered early (before the development of intestinal metaplasia). Among H. pylori-infected patients, those who receive long-term treatment with proton pump inhibitors more frequently develop preneoplastic lesions. In patients who undergo endoscopic resection of early gastric cancer, H. pylori eradication reduces the incidence of metachronous tumors. Eradication therapy induces regression of MALT lymphoma in most patients and tumoral recurrence in the long term is exceptional; eradication is a reasonable option even when H. pylori infection has not been identified in patients with MALT lymphoma. Several diagnostic innovations were presented, such as some polymerase chain reaction techniques for use in gastric biopsy specimens or gastric juice. The efficacy of triple standard therapy is clearly inadequate. The superiority of "sequential" therapy over standard triple therapy has not been definitively established. "Concomitant" therapy is more effective and is simpler than "sequential" therapy. After failure of standard triple therapy, second-line levofloxacin-based schemes for 10 days are effective and are also simpler and better tolerated than bismuth-based quadruple therapy. Levofloxacin-based triple therapy is also a promising alternative after failure of "sequential" and "concomitant" therapies. New-generation quinolones, such as moxifloxacin, could be useful as eradication therapy, especially as rescue therapy. After failure of clarithromycin-based triple therapy, followed by that of levofloxacin-based triple therapy, a bismuth-based quadruple scheme is an acceptable alternative. Even after the failure of 3 eradication therapies, a fourth empirical rescue therapy (with rifabutin) can be effective. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Proton Therapy Dose Characterization and Verification

DTIC Science & Technology

2013-10-01

predefined acceptance criteria. The Calypso System accurately localizes LT and LO patients in the IBA proton therapy vault at the University of Pennsylvania...earlier vet>ions of mdioct.’omio 0 lm. Thcrr ’" Jechnkul 1\\Sues ~nd challenge~ tluu mu.~t be ad~ts:led and rrsolvtd pnor lo Ibm nppllculion for do...IOcmatthch«enter) from a Varian l100linc1!r aecdcmtur (llnac) dirr<ltd plll’nllel lo nn EBTI film ~nd wtchtd bCiwttn slit!• of ••.lhd wurcr1 M. The plwuom

Investigating CT to CBCT image registration for head and neck proton therapy as a tool for daily dose recalculation

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

Landry, Guillaume, E-mail: g.landry@lmu.de; Nijhuis, Reinoud; Thieke, Christian

2015-03-15

Purpose: Intensity modulated proton therapy (IMPT) of head and neck (H and N) cancer patients may be improved by plan adaptation. The decision to adapt the treatment plan based on a dose recalculation on the current anatomy requires a diagnostic quality computed tomography (CT) scan of the patient. As gantry-mounted cone beam CT (CBCT) scanners are currently being offered by vendors, they may offer daily or weekly updates of patient anatomy. CBCT image quality may not be sufficient for accurate proton dose calculation and it is likely necessary to perform CBCT CT number correction. In this work, the authors investigatedmore » deformable image registration (DIR) of the planning CT (pCT) to the CBCT to generate a virtual CT (vCT) to be used for proton dose recalculation. Methods: Datasets of six H and N cancer patients undergoing photon intensity modulated radiation therapy were used in this study to validate the vCT approach. Each dataset contained a CBCT acquired within 3 days of a replanning CT (rpCT), in addition to a pCT. The pCT and rpCT were delineated by a physician. A Morphons algorithm was employed in this work to perform DIR of the pCT to CBCT following a rigid registration of the two images. The contours from the pCT were deformed using the vector field resulting from DIR to yield a contoured vCT. The DIR accuracy was evaluated with a scale invariant feature transform (SIFT) algorithm comparing automatically identified matching features between vCT and CBCT. The rpCT was used as reference for evaluation of the vCT. The vCT and rpCT CT numbers were converted to stopping power ratio and the water equivalent thickness (WET) was calculated. IMPT dose distributions from treatment plans optimized on the pCT were recalculated with a Monte Carlo algorithm on the rpCT and vCT for comparison in terms of gamma index, dose volume histogram (DVH) statistics as well as proton range. The DIR generated contours on the vCT were compared to physician-drawn contours on the rpCT. Results: The DIR accuracy was better than 1.4 mm according to the SIFT evaluation. The mean WET differences between vCT (pCT) and rpCT were below 1 mm (2.6 mm). The amount of voxels passing 3%/3 mm gamma criteria were above 95% for the vCT vs rpCT. When using the rpCT contour set to derive DVH statistics from dose distributions calculated on the rpCT and vCT the differences, expressed in terms of 30 fractions of 2 Gy, were within [−4, 2 Gy] for parotid glands (D{sub mean}), spinal cord (D{sub 2%}), brainstem (D{sub 2%}), and CTV (D{sub 95%}). When using DIR generated contours for the vCT, those differences ranged within [−8, 11 Gy]. Conclusions: In this work, the authors generated CBCT based stopping power distributions using DIR of the pCT to a CBCT scan. DIR accuracy was below 1.4 mm as evaluated by the SIFT algorithm. Dose distributions calculated on the vCT agreed well to those calculated on the rpCT when using gamma index evaluation as well as DVH statistics based on the same contours. The use of DIR generated contours introduced variability in DVH statistics.« less

Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy.

PubMed

Flejmer, Anna M; Edvardsson, Anneli; Dohlmar, Frida; Josefsson, Dan; Nilsson, Mats; Witt Nyström, Petra; Dasu, Alexandru

2016-05-01

Background Respiratory gating and proton therapy have both been proposed to reduce the cardiopulmonary burden in breast cancer radiotherapy. This study aims to investigate the additional benefit of proton radiotherapy for breast cancer with and without respiratory gating. Material and methods Twenty left-sided patients were planned on computed tomography (CT)-datasets acquired during enhanced inspiration gating (EIG) and free-breathing (FB), using photon three-dimensional conformal radiation therapy (3D-CRT) and scanned proton beams. Ten patients received treatment to the whole breast only (WBO) and 10 were treated to the breast and the regional lymph nodes (BRN). Dosimetric parameters characterizing the coverage of target volumes and the cardiopulmonary burden were compared using a paired, two-tailed Student's t-test. Results Protons ensured comparable or better target coverage than photons in all patients during both EIG and FB. The heterogeneity index decreased from 12% with photons to about 5% with protons. The mean dose to the ipsilateral lung was reduced in BRN patients from 12 Gy to 7 Gy  (RBE) in EIG and from 14 Gy to 6-7 Gy (RBE) in FB, while for WBO patients all values were about 5-6 Gy (RBE). The mean dose to heart decreased by a factor of four in WBO patients [from 1.1 Gy to 0.3 Gy (RBE) in EIG and from 2.1 Gy to 0.5 Gy (RBE) in FB] and 10 in BRN patients [from 2.1 Gy to 0.2 Gy (RBE) in EIG and from 3.4 Gy to 0.3 Gy (RBE) in FB]. Similarly, the mean and the near maximum dose to the left anterior descending artery (LAD) were significantly lower (p < 0.05) with protons in comparison with photons. Conclusion Proton spot scanning has a high potential to reduce the irradiation of organs at risk and other normal tissues for most patients, beyond what could be achieved with EIG and photon therapy. The largest dose sparing has been seen for BRN patients, both in terms of cardiopulmonary burden and integral dose.

Modelling PET radionuclide production in tissue and external targets using Geant4

NASA Astrophysics Data System (ADS)

Amin, T.; Infantino, A.; Lindsay, C.; Barlow, R.; Hoehr, C.

2017-07-01

The Proton Therapy Facility in TRIUMF provides 74 MeV protons extracted from a 500 MeV H- cyclotron for ocular melanoma treatments. During treatment, positron emitting radionuclides such as 1C, 15O and 13N are produced in patient tissue. Using PET scanners, the isotopic activity distribution can be measured for in-vivo range verification. A second cyclotron, the TR13, provides 13 MeV protons onto liquid targets for the production of PET radionuclides such as 18F, 13N or 68Ga, for medical applications. The aim of this work was to validate Geant4 against FLUKA and experimental measurements for production of the above-mentioned isotopes using the two cyclotrons. The results show variable degrees of agreement. For proton therapy, the proton-range agreement was within 2 mm for 11C activity, whereas 13N disagreed. For liquid targets at the TR13 the average absolute deviation ratio between FLUKA and experiment was 1.9±2.7, whereas the average absolute deviation ratio between Geant4 and experiment was 0. 6±0.4. This is due to the uncertainties present in experimentally determined reaction cross sections.

Experimental validation of a Monte Carlo proton therapy nozzle model incorporating magnetically steered protons.

PubMed

Peterson, S W; Polf, J; Bues, M; Ciangaru, G; Archambault, L; Beddar, S; Smith, A

2009-05-21

The purpose of this study is to validate the accuracy of a Monte Carlo calculation model of a proton magnetic beam scanning delivery nozzle developed using the Geant4 toolkit. The Monte Carlo model was used to produce depth dose and lateral profiles, which were compared to data measured in the clinical scanning treatment nozzle at several energies. Comparisons were also made between measured and simulated off-axis profiles to test the accuracy of the model's magnetic steering. Comparison of the 80% distal dose fall-off values for the measured and simulated depth dose profiles agreed to within 1 mm for the beam energies evaluated. Agreement of the full width at half maximum values for the measured and simulated lateral fluence profiles was within 1.3 mm for all energies. The position of measured and simulated spot positions for the magnetically steered beams agreed to within 0.7 mm of each other. Based on these results, we found that the Geant4 Monte Carlo model of the beam scanning nozzle has the ability to accurately predict depth dose profiles, lateral profiles perpendicular to the beam axis and magnetic steering of a proton beam during beam scanning proton therapy.

Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.

PubMed

García-Rayado, Guillermo; Sostres, Carlos; Lanas, Angel

2017-08-01

Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

NASA Astrophysics Data System (ADS)

Adam, J.; Adamová, D.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Agrawal, N.; Ahammed, Z.; Ahmad, S.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Alam, S. N.; Albuquerque, D. S. D.; Aleksandrov, D.; Alessandro, B.; Alexandre, D.; Molina, R. Alfaro; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altinpinar, S.; Altsybeev, I.; Prado, C. Alves Garcia; An, M.; Andrei, C.; Andrews, H. A.; Andronic, A.; Anguelov, V.; Antičić, T.; Antinori, F.; Antonioli, P.; Aphecetche, L.; Appelshäuser, H.; Arcelli, S.; Arnaldi, R.; Arnold, O. W.; Arsene, I. C.; Arslandok, M.; Audurier, B.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badalà, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Balasubramanian, S.; Baldisseri, A.; Baral, R. C.; Barbano, A. M.; Barbera, R.; Barile, F.; Barnaföldi, G. G.; Barnby, L. S.; Barret, V.; Bartalini, P.; Barth, K.; Bartke, J.; Bartsch, E.; Basile, M.; Bastid, N.; Basu, S.; Bathen, B.; Batigne, G.; Camejo, A. Batista; Batyunya, B.; Batzing, P. C.; Bearden, I. G.; Beck, H.; Bedda, C.; Behera, N. K.; Belikov, I.; Bellini, F.; Martinez, H. Bello; Bellwied, R.; Belmont, R.; Belmont-Moreno, E.; Beltran, L. G. E.; Belyaev, V.; Bencedi, G.; Beole, S.; Berceanu, I.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhati, A. K.; Bhattacharjee, B.; Bhom, J.; Bianchi, L.; Bianchi, N.; Bianchin, C.; Bielčík, J.; Bielčíková, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Bjelogrlic, S.; Blair, J. T.; Blau, D.; Blume, C.; Bock, F.; Bogdanov, A.; Bøggild, H.; Boldizsár, L.; Bombara, M.; Bonora, M.; Book, J.; Borel, H.; Borissov, A.; Borri, M.; Bossú, F.; Botta, E.; Bourjau, C.; Braun-Munzinger, P.; Bregant, M.; Breitner, T.; Broker, T. A.; Browning, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Cabala, J.; Caffarri, D.; Cai, X.; Caines, H.; Diaz, L. Calero; Caliva, A.; Villar, E. Calvo; Camerini, P.; Carena, F.; Carena, W.; Carnesecchi, F.; Castellanos, J. Castillo; Castro, A. J.; Casula, E. A. R.; Sanchez, C. Ceballos; Cepila, J.; Cerello, P.; Cerkala, J.; Chang, B.; Chapeland, S.; Chartier, M.; Charvet, J. L.; Chattopadhyay, S.; Chattopadhyay, S.; Chauvin, A.; Chelnokov, V.; Cherney, M.; Cheshkov, C.; Cheynis, B.; Barroso, V. Chibante; Chinellato, D. D.; Cho, S.; Chochula, P.; Choi, K.; Chojnacki, M.; Choudhury, S.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Chung, S. U.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Balbastre, G. Conesa; Del Valle, Z. Conesa; Connors, M. E.; Contreras, J. G.; Cormier, T. M.; Morales, Y. Corrales; Maldonado, I. Cortés; Cortese, P.; Cosentino, M. R.; Costa, F.; Crkovska, J.; Crochet, P.; Albino, R. Cruz; Cuautle, E.; Cunqueiro, L.; Dahms, T.; Dainese, A.; Danisch, M. C.; Danu, A.; Das, D.; Das, I.; Das, S.; Dash, A.; Dash, S.; de, S.; de Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; de Falco, A.; de Gruttola, D.; De Marco, N.; de Pasquale, S.; de Souza, R. D.; Deisting, A.; Deloff, A.; Dénes, E.; Deplano, C.; Dhankher, P.; di Bari, D.; di Mauro, A.; di Nezza, P.; di Ruzza, B.; Corchero, M. A. Diaz; Dietel, T.; Dillenseger, P.; Divià, R.; Djuvsland, Ø.; Dobrin, A.; Gimenez, D. Domenicis; Dönigus, B.; Dordic, O.; Drozhzhova, T.; Dubey, A. K.; Dubla, A.; Ducroux, L.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Endress, E.; Engel, H.; Epple, E.; Erazmus, B.; Erdemir, I.; Erhardt, F.; Espagnon, B.; Estienne, M.; Esumi, S.; Eum, J.; Evans, D.; Evdokimov, S.; Eyyubova, G.; Fabbietti, L.; Fabris, D.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Ferencei, J.; Téllez, A. Fernández; Ferreiro, E. G.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Figueredo, M. A. S.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiore, E. M.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francescon, A.; Francisco, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Girard, M. Fusco; Gaardhøje, J. J.; Gagliardi, M.; Gago, A. M.; Gajdosova, K.; Gallio, M.; Galvan, C. D.; Gangadharan, D. R.; Ganoti, P.; Gao, C.; Garabatos, C.; Garcia-Solis, E.; Garg, K.; Gargiulo, C.; Gasik, P.; Gauger, E. F.; Germain, M.; Gheata, M.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Gladysz-Dziadus, E.; Glässel, P.; Coral, D. M. Goméz; Ramirez, A. Gomez; Gonzalez, A. S.; Gonzalez, V.; González-Zamora, P.; Gorbunov, S.; Görlich, L.; Gotovac, S.; Grabski, V.; Grachov, O. A.; Graczykowski, L. K.; Graham, K. L.; Grelli, A.; Grigoras, A.; Grigoras, C.; Grigoriev, V.; Grigoryan, A.; Grigoryan, S.; Grinyov, B.; Grion, N.; Gronefeld, J. M.; Grosse-Oetringhaus, J. F.; Grosso, R.; Gruber, L.; Guber, F.; Guernane, R.; Guerzoni, B.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Gupta, R.; Haake, R.; Hadjidakis, C.; Haiduc, M.; Hamagaki, H.; Hamar, G.; Hamon, J. C.; Harris, J. W.; Harton, A.; Hatzifotiadou, D.; Hayashi, S.; Heckel, S. T.; Hellbär, E.; Helstrup, H.; Herghelegiu, A.; Corral, G. Herrera; Herrmann, F.; Hess, B. A.; Hetland, K. F.; Hillemanns, H.; Hippolyte, B.; Horak, D.; Hosokawa, R.; Hristov, P.; Hughes, C.; Humanic, T. J.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Ilkaev, R.; Inaba, M.; Incani, E.; Ippolitov, M.; Irfan, M.; Isakov, V.; Ivanov, M.; Ivanov, V.; Izucheev, V.; Jacak, B.; Jacazio, N.; Jacobs, P. M.; Jadhav, M. B.; Jadlovska, S.; Jadlovsky, J.; Jahnke, C.; Jakubowska, M. J.; Janik, M. A.; Jayarathna, P. H. S. Y.; Jena, C.; Jena, S.; Bustamante, R. T. Jimenez; Jones, P. G.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kang, J. H.; Kaplin, V.; Kar, S.; Uysal, A. Karasu; Karavichev, O.; Karavicheva, T.; Karayan, L.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keijdener, D. L. D.; Keil, M.; Khan, M. Mohisin; Khan, P.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Khatun, A.; Kileng, B.; Kim, D. W.; Kim, D. J.; Kim, D.; Kim, H.; Kim, J. S.; Kim, J.; Kim, M.; Kim, S.; Kim, T.; Kirsch, S.; Kisel, I.; Kiselev, S.; Kisiel, A.; Kiss, G.; Klay, J. L.; Klein, C.; Klein, J.; Klein-Bösing, C.; Klewin, S.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobdaj, C.; Kofarago, M.; Kollegger, T.; Kolojvari, A.; Kondratiev, V.; Kondratyeva, N.; Kondratyuk, E.; Konevskikh, A.; Kopcik, M.; Kour, M.; Kouzinopoulos, C.; Kovalenko, O.; Kovalenko, V.; Kowalski, M.; Meethaleveedu, G. Koyithatta; Králik, I.; Kravčáková, A.; Krivda, M.; Krizek, F.; Kryshen, E.; Krzewicki, M.; Kubera, A. M.; Kučera, V.; Kuhn, C.; Kuijer, P. G.; Kumar, A.; Kumar, J.; Kumar, L.; Kumar, S.; Kurashvili, P.; Kurepin, A.; Kurepin, A. B.; Kuryakin, A.; Kweon, M. J.; Kwon, Y.; La Pointe, S. L.; La Rocca, P.; de Guevara, P. Ladron; Fernandes, C. Lagana; Lakomov, I.; Langoy, R.; Lapidus, K.; Lara, C.; Lardeux, A.; Lattuca, A.; Laudi, E.; Lea, R.; Leardini, L.; Lee, S.; Lehas, F.; Lehner, S.; Lemmon, R. C.; Lenti, V.; Leogrande, E.; Monzón, I. León; Vargas, H. León; Leoncino, M.; Lévai, P.; Li, S.; Li, X.; Lien, J.; Lietava, R.; Lindal, S.; Lindenstruth, V.; Lippmann, C.; Lisa, M. A.; Ljunggren, H. M.; Lodato, D. F.; Loenne, P. I.; Loginov, V.; Loizides, C.; Lopez, X.; Torres, E. López; Lowe, A.; Luettig, P.; Lunardon, M.; Luparello, G.; Lupi, M.; Lutz, T. H.; Maevskaya, A.; Mager, M.; Mahajan, S.; Mahmood, S. M.; Maire, A.; Majka, R. D.; Malaev, M.; Cervantes, I. Maldonado; Malinina, L.; Mal'Kevich, D.; Malzacher, P.; Mamonov, A.; Manko, V.; Manso, F.; Manzari, V.; Mao, Y.; Marchisone, M.; Mareš, J.; Margagliotti, G. V.; Margotti, A.; Margutti, J.; Marín, A.; Markert, C.; Marquard, M.; Martin, N. A.; Martinengo, P.; Martínez, M. I.; García, G. Martínez; Pedreira, M. Martinez; Mas, A.; Masciocchi, S.; Masera, M.; Masoni, A.; Mastroserio, A.; Matyja, A.; Mayer, C.; Mazer, J.; Mazzilli, M.; Mazzoni, M. A.; McDonald, D.; Meddi, F.; Melikyan, Y.; Menchaca-Rocha, A.; Meninno, E.; Pérez, J. Mercado; Meres, M.; Mhlanga, S.; Miake, Y.; Mieskolainen, M. M.; Mikhaylov, K.; Milano, L.; Milosevic, J.; Mischke, A.; Mishra, A. N.; Mishra, T.; Miśkowiec, D.; Mitra, J.; Mitu, C. M.; Mohammadi, N.; Mohanty, B.; Molnar, L.; Zetina, L. Montaño; Montes, E.; de Godoy, D. A. Moreira; Moreno, L. A. P.; Moretto, S.; Morreale, A.; Morsch, A.; Muccifora, V.; Mudnic, E.; Mühlheim, D.; Muhuri, S.; Mukherjee, M.; Mulligan, J. D.; Munhoz, M. G.; Münning, K.; Munzer, R. H.; Murakami, H.; Murray, S.; Musa, L.; Musinsky, J.; Naik, B.; Nair, R.; Nandi, B. K.; Nania, R.; Nappi, E.; Naru, M. U.; da Luz, H. Natal; Nattrass, C.; Navarro, S. R.; Nayak, K.; Nayak, R.; Nayak, T. K.; Nazarenko, S.; Nedosekin, A.; de Oliveira, R. A. Negrao; Nellen, L.; Ng, F.; Nicassio, M.; Niculescu, M.; Niedziela, J.; Nielsen, B. S.; Nikolaev, S.; Nikulin, S.; Nikulin, V.; Noferini, F.; Nomokonov, P.; Nooren, G.; Noris, J. C. C.; Norman, J.; Nyanin, A.; Nystrand, J.; Oeschler, H.; Oh, S.; Oh, S. K.; Ohlson, A.; Okatan, A.; Okubo, T.; Oleniacz, J.; da Silva, A. C. Oliveira; Oliver, M. H.; Onderwaater, J.; Oppedisano, C.; Orava, R.; Oravec, M.; Velasquez, A. Ortiz; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Ozdemir, M.; Pachmayer, Y.; Pagano, D.; Pagano, P.; Paić, G.; Pal, S. K.; Palni, P.; Pan, J.; Pandey, A. K.; Papikyan, V.; Pappalardo, G. S.; Pareek, P.; Park, W. J.; Parmar, S.; Passfeld, A.; Paticchio, V.; Patra, R. N.; Paul, B.; Pei, H.; Peitzmann, T.; Peng, X.; da Costa, H. Pereira; Peresunko, D.; Lezama, E. Perez; Peskov, V.; Pestov, Y.; Petráček, V.; Petrov, V.; Petrovici, M.; Petta, C.; Piano, S.; Pikna, M.; Pillot, P.; Pimentel, L. O. D. L.; Pinazza, O.; Pinsky, L.; Piyarathna, D. B.; Płoskoń, M.; Planinic, M.; Pluta, J.; Pochybova, S.; Podesta-Lerma, P. L. M.; Poghosyan, M. G.; Polichtchouk, B.; Poljak, N.; Poonsawat, W.; Pop, A.; Poppenborg, H.; Porteboeuf-Houssais, S.; Porter, J.; Pospisil, J.; Prasad, S. K.; Preghenella, R.; Prino, F.; Pruneau, C. A.; Pshenichnov, I.; Puccio, M.; Puddu, G.; Pujahari, P.; Punin, V.; Putschke, J.; Qvigstad, H.; Rachevski, A.; Raha, S.; Rajput, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Rami, F.; Raniwala, R.; Raniwala, S.; Räsänen, S. S.; Rascanu, B. T.; Rathee, D.; Ravasenga, I.; Read, K. F.; Redlich, K.; Reed, R. J.; Rehman, A.; Reichelt, P.; Reidt, F.; Ren, X.; Renfordt, R.; Reolon, A. R.; Reshetin, A.; Reygers, K.; Riabov, V.; Ricci, R. A.; Richert, T.; Richter, M.; Riedler, P.; Riegler, W.; Riggi, F.; Ristea, C.; Cahuantzi, M. Rodríguez; Manso, A. Rodriguez; Røed, K.; Rogochaya, E.; Rohr, D.; Röhrich, D.; Ronchetti, F.; Ronflette, L.; Rosnet, P.; Rossi, A.; Roukoutakis, F.; Roy, A.; Roy, C.; Roy, P.; Montero, A. J. Rubio; Rui, R.; Russo, R.; Ryabinkin, E.; Ryabov, Y.; Rybicki, A.; Saarinen, S.; Sadhu, S.; Sadovsky, S.; Šafařík, K.; Sahlmuller, B.; Sahoo, P.; Sahoo, R.; Sahoo, S.; Sahu, P. K.; Saini, J.; Sakai, S.; Saleh, M. A.; Salzwedel, J.; Sambyal, S.; Samsonov, V.; Šándor, L.; Sandoval, A.; Sano, M.; Sarkar, D.; Sarkar, N.; Sarma, P.; Scapparone, E.; Scarlassara, F.; Schiaua, C.; Schicker, R.; Schmidt, C.; Schmidt, H. R.; Schmidt, M.; Schuchmann, S.; Schukraft, J.; Schutz, Y.; Schwarz, K.; Schweda, K.; Scioli, G.; Scomparin, E.; Scott, R.; Šefčík, M.; Seger, J. E.; Sekiguchi, Y.; Sekihata, D.; Selyuzhenkov, I.; Senosi, K.; Senyukov, S.; Serradilla, E.; Sevcenco, A.; Shabanov, A.; Shabetai, A.; Shadura, O.; Shahoyan, R.; Shangaraev, A.; Sharma, A.; Sharma, M.; Sharma, M.; Sharma, N.; Sheikh, A. I.; Shigaki, K.; Shou, Q.; Shtejer, K.; Sibiriak, Y.; Siddhanta, S.; Sielewicz, K. M.; Siemiarczuk, T.; Silvermyr, D.; Silvestre, C.; Simatovic, G.; Simonetti, G.; Singaraju, R.; Singh, R.; Singhal, V.; Sinha, T.; Sitar, B.; Sitta, M.; Skaali, T. B.; Slupecki, M.; Smirnov, N.; Snellings, R. J. M.; Snellman, T. W.; Song, J.; Song, M.; Song, Z.; Soramel, F.; Sorensen, S.; Sozzi, F.; Spiriti, E.; Sputowska, I.; Spyropoulou-Stassinaki, M.; Stachel, J.; Stan, I.; Stankus, P.; Stenlund, E.; Steyn, G.; Stiller, J. H.; Stocco, D.; Strmen, P.; Suaide, A. A. P.; Sugitate, T.; Suire, C.; Suleymanov, M.; Suljic, M.; Sultanov, R.; Šumbera, M.; Sumowidagdo, S.; Swain, S.; Szabo, A.; Szarka, I.; Szczepankiewicz, A.; Szymanski, M.; Tabassam, U.; Takahashi, J.; Tambave, G. J.; Tanaka, N.; Tarhini, M.; Tariq, M.; Tarzila, M. G.; Tauro, A.; Muñoz, G. Tejeda; Telesca, A.; Terasaki, K.; Terrevoli, C.; Teyssier, B.; Thäder, J.; Thakur, D.; Thomas, D.; Tieulent, R.; Tikhonov, A.; Timmins, A. R.; Toia, A.; Trogolo, S.; Trombetta, G.; Trubnikov, V.; Trzaska, W. H.; Tsuji, T.; Tumkin, A.; Turrisi, R.; Tveter, T. S.; Ullaland, K.; Uras, A.; Usai, G. L.; Utrobicic, A.; Vala, M.; Palomo, L. Valencia; van der Maarel, J.; van Hoorne, J. W.; van Leeuwen, M.; Vanat, T.; Vyvre, P. Vande; Varga, D.; Vargas, A.; Vargyas, M.; Varma, R.; Vasileiou, M.; Vasiliev, A.; Vauthier, A.; Doce, O. Vázquez; Vechernin, V.; Veen, A. M.; Velure, A.; Vercellin, E.; Limón, S. Vergara; Vernet, R.; Vickovic, L.; Viinikainen, J.; Vilakazi, Z.; Baillie, O. Villalobos; Tello, A. Villatoro; Vinogradov, A.; Vinogradov, L.; Virgili, T.; Vislavicius, V.; Viyogi, Y. P.; Vodopyanov, A.; Völkl, M. A.; Voloshin, K.; Voloshin, S. A.; Volpe, G.; von Haller, B.; Vorobyev, I.; Vranic, D.; Vrláková, J.; Vulpescu, B.; Wagner, B.; Wagner, J.; Wang, H.; Wang, M.; Watanabe, D.; Watanabe, Y.; Weber, M.; Weber, S. G.; Weiser, D. F.; Wessels, J. P.; Westerhoff, U.; Whitehead, A. M.; Wiechula, J.; Wikne, J.; Wilk, G.; Wilkinson, J.; Willems, G. A.; Williams, M. C. S.; Windelband, B.; Winn, M.; Yalcin, S.; Yang, P.; Yano, S.; Yin, Z.; Yokoyama, H.; Yoo, I.-K.; Yoon, J. H.; Yurchenko, V.; Zaborowska, A.; Zaccolo, V.; Zaman, A.; Zampolli, C.; Zanoli, H. J. C.; Zaporozhets, S.; Zardoshti, N.; Zarochentsev, A.; Závada, P.; Zaviyalov, N.; Zbroszczyk, H.; Zgura, I. S.; Zhalov, M.; Zhang, H.; Zhang, X.; Zhang, Y.; Zhang, C.; Zhang, Z.; Zhao, C.; Zhigareva, N.; Zhou, D.; Zhou, Y.; Zhou, Z.; Zhu, H.; Zhu, J.; Zichichi, A.; Zimmermann, A.; Zimmermann, M. B.; Zinovjev, G.; Zyzak, M.

2017-06-01

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed. Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions, is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions, but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results, indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.

Measurements of neutron dose equivalent for a proton therapy center using uniform scanning proton beams

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

Zheng Yuanshui; Liu Yaxi; Zeidan, Omar

Purpose: Neutron exposure is of concern in proton therapy, and varies with beam delivery technique, nozzle design, and treatment conditions. Uniform scanning is an emerging treatment technique in proton therapy, but neutron exposure for this technique has not been fully studied. The purpose of this study is to investigate the neutron dose equivalent per therapeutic dose, H/D, under various treatment conditions for uniform scanning beams employed at our proton therapy center. Methods: Using a wide energy neutron dose equivalent detector (SWENDI-II, ThermoScientific, MA), the authors measured H/D at 50 cm lateral to the isocenter as a function of proton range,more » modulation width, beam scanning area, collimated field size, and snout position. They also studied the influence of other factors on neutron dose equivalent, such as aperture material, the presence of a compensator, and measurement locations. They measured H/D for various treatment sites using patient-specific treatment parameters. Finally, they compared H/D values for various beam delivery techniques at various facilities under similar conditions. Results: H/D increased rapidly with proton range and modulation width, varying from about 0.2 mSv/Gy for a 5 cm range and 2 cm modulation width beam to 2.7 mSv/Gy for a 30 cm range and 30 cm modulation width beam when 18 Multiplication-Sign 18 cm{sup 2} uniform scanning beams were used. H/D increased linearly with the beam scanning area, and decreased slowly with aperture size and snout retraction. The presence of a compensator reduced the H/D slightly compared with that without a compensator present. Aperture material and compensator material also have an influence on neutron dose equivalent, but the influence is relatively small. H/D varied from about 0.5 mSv/Gy for a brain tumor treatment to about 3.5 mSv/Gy for a pelvic case. Conclusions: This study presents H/D as a function of various treatment parameters for uniform scanning proton beams. For similar treatment conditions, the H/D value per uncollimated beam size for uniform scanning beams was slightly lower than that from a passive scattering beam and higher than that from a pencil beam scanning beam, within a factor of 2. Minimizing beam scanning area could effectively reduce neutron dose equivalent for uniform scanning beams, down to the level close to pencil beam scanning.« less

Proton beam dosimetry: a comparison between a plastic scintillator, ionization chamber and Faraday cup.

PubMed

Ghergherehchi, Mitra; Afarideh, Hossein; Ghannadi, Mohammad; Mohammadzadeh, Ahmad; Aslani, Golam Reza; Boghrati, Behzad

2010-01-01

In this study, a comparison was made between a plastic scintillator (BC400), a Faraday Cup (FC) and an ionization chamber (IC) used for routine proton dosimetry. Thin scintillators can be applied to proton dosimetry and consequently to proton therapy as relative dosimeters because of their water-equivalent nature, high energy-light conversion efficiency, low dimensions and good proportionality to the absorbed dose at low stopping powers. To employ such scintillators as relative dosimeters in proton therapy, the corrective factors must be applied to correct the quenching luminescence at the Bragg peak. A fine linear proportionality between the luminescence light yield Y and the proton flux in a thin (0.5 mm) scintillator for the 20 and 30 MeV proton beams were observed. The experimental peak/plateau ratios of Bragg Curve for 2, 1 and 0.5 mm scintillators with an accuracy of 0.5% were obtained to be 1.87, 1.91 and 2.30, respectively. With combination of the Markus chamber and the CR-39 detector, the peak/plateau ratio was improved to 3.26. The obtained data of the luminescence yield as a function of the specific energy loss is in agreement with the Craun-Birk's theory. Results show that the FC and Markus ionization chamber are in agreement within 4%, while the FC gives a lower dose evaluation. For a defined beam, the data for the fluence measurements are reproducible within a good accuracy.

SU-F-T-131: No Increase in Biological Effectiveness Through Collimator Scattered Low Energy Protons

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

Matsuura, T; Takao, S; Matsuzaki, Y

Purpose: To reduce the lateral penumbra of low-energy proton beams, brass collimators are often used in spot-scanning proton therapy (SSPT). This study investigates the increase in biological effectiveness through collimator scattered protons in SSPT. Methods: The SSPT system of the Hokkaido University Hospital Proton Beam Therapy Center, which consists of a scanning nozzle, a 2-cm thick brass collimator, and a 4-cm thick energy absorber, was simulated with our validated Geant4 Monte Carlo code (ver. 9.3). A water phantom was irradiated with proton pencil beams of 76, 110, and 143 MeV. The tested collimator opening areas (COA) were 5×5, 10×10, andmore » 15×15 cm{sup 2}. Comparisons were made among the dose-averaged LET values of protons that hit the collimators (LETDColl), protons that did not hit the collimators (LETDNoColl), and all protons (LETDTotal). X-ray equivalent doses (Deq) were calculated using the linear-quadratic model with LETDNoColl and LETDTotal, and their maximum difference was determined over regions where the physical dose was greater than 10% of the peak dose of 2 Gy. Results: The ratio of the dose contribution of collimator scattered protons to that of all protons, defined as λ, was large at high proton energies and large COAs. The maximum λ value ranged from 3% (76 MeV, 5×5 cm{sup 2}) to 29% (143 MeV, 15×15 cm{sup 2}). Moreover, a large difference between LETDColl and LETDNoColl was only found in regions where λ was below 20% (ΔLETD > 2 keV/µm) and 8% (ΔLETD > 5 keV/µm). Consequently, the maximum difference between LETDNoColl and LETDTotal was as small as 0.8 keV/µm in all simulated voxels, and the difference of Deq reached a maximum of 1.5% that of the peak dose obtained at the water surface with a 76 MeV beam. Conclusion: Although collimator scattered protons have high LET, they only increase the physical dose, not the biological effectiveness.« less

Outcomes of Proton Therapy for Patients With Functional Pituitary Adenomas

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

Wattson, Daniel A.; Tanguturi, Shyam K.; Spiegel, Daphna Y.

2014-11-01

Purpose/Objective(s): This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs). Methods and Materials: We analyzed 165 patients with FPAs who were treated at a single institution with proton therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥3 months of normal laboratory values with no medical treatment), local control,more » and adverse effects are reported. Results: With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone—secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors. Conclusions: Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary adverse effect.« less

First steps towards a gas-phase acidity ladder for derivatized fullerene dications

NASA Astrophysics Data System (ADS)

Petrie, Simon; Javahery, Gholamreza; Bohme, Diethard K.

1993-03-01

C2+60 can be derivatized by gas-phase ion/molecule reactions with polar hydrogen-bearing molecules. The adduct dications so produced may then undergo proton transfer to neutrals. The occurrence or absence of proton transfer as a secondary process gives information on the gas-phase acidity of the dicationic species C60·(XH)2+in. We have performed studies using a selected-ion flow tube at 294 ± 2 K and 0.35 ± 0.01 Torr, and have used observed reactivity of such dicationic fullerene adducts to determine upper or lower limits to their apparent and absolute gas-phase acidities. We present also a rationale for assessing the proton-transfer reactivity of dications via the apparent gas-phase acidity of these species, rather than the traditional use of gas-phase basicities or proton affinities. We propose that further studies of proton transfer from polycharged fullerene adducts may provide considerable useful information to model the reactivity of polyprotonated proteins and other large molecular polycatiions which can now be produced by techniques such as electrospray ionization.

Theoretical investigation of low detection sensitivity for underivatized carbohydrates in ESI and MALDI.

PubMed

Chen, Jien-Lian; Lee, Chuping; Lu, I-Chung; Chien, Chia-Lung; Lee, Yuan-Tseh; Hu, Wei-Ping; Ni, Chi-Kung

2016-12-01

Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) mainly generate protonated ions from peptides and proteins but sodiated (or potassiated) ions from carbohydrates. The ion intensities of sodiated (or potassiated) carbohydrates generated by ESI and MALDI are generally lower than those of protonated peptides and proteins. Ab initio calculations and transition state theory were used to investigate the reasons for the low detection sensitivity for underivatized carbohydrates. We used glucose and cellobiose as examples and showed that the low detection sensitivity is partly attributable to the following factors. First, glucose exhibits a low proton affinity. Most protons generated by ESI or MALDI attach to water clusters and matrix molecules. Second, protonated glucose and cellobiose can easily undergo dehydration reactions. Third, the sodiation affinities of glucose and cellobiose are small. Some sodiated glucose and cellobiose dissociate into the sodium cations and neutral carbohydrates during ESI or MALDI process. The increase of detection sensitivity of carbohydrates in mass spectrometry by various methods can be rationalized according to these factors. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A treatment planning study to assess the feasibility of laser-driven proton therapy using a compact gantry design.

PubMed

Hofmann, Kerstin M; Masood, Umar; Pawelke, Joerg; Wilkens, Jan J

2015-09-01

Laser-driven proton acceleration is suggested as a cost- and space-efficient alternative for future radiation therapy centers, although the properties of these beams are fairly different compared to conventionally accelerated proton beams. The laser-driven proton beam is extremely pulsed containing a very high proton number within ultrashort bunches at low bunch repetition rates of few Hz and the energy spectrum of the protons per bunch is very broad. Moreover, these laser accelerated bunches are subject to shot-to-shot fluctuations. Therefore, the aim of this study was to investigate the feasibility of a compact gantry design for laser-driven proton therapy and to determine limitations to comply with. Based on a published gantry beam line design which can filter parabolic spectra from an exponentially decaying broad initial spectrum, a treatment planning study was performed on real patient data sets. All potential parabolic spectra were fed into a treatment planning system and numerous spot scanning proton plans were calculated. To investigate limitations in the fluence per bunch, the proton number of the initial spectrum and the beam width at patient entrance were varied. A scenario where only integer shots are delivered as well as an intensity modulation from shot to shot was studied. The resulting plans were evaluated depending on their dosimetric quality and in terms of required treatment time. In addition, the influence of random shot-to-shot fluctuations on the plan quality was analyzed. The study showed that clinically relevant dose distributions can be produced with the system under investigation even with integer shots. For small target volumes receiving high doses per fraction, the initial proton number per bunch must remain between 1.4 × 10(8) and 8.3 × 10(9) to achieve acceptable delivery times as well as plan qualities. For larger target volumes and standard doses per fraction, the initial proton number is even more restricted to stay between 1.4 × 10(9) and 2.9 × 10(9). The lowest delivery time that could be reached for such a case was 16 min for a 10 Hz system. When modulating the intensity from shot to shot, the delivery time can be reduced to 6 min for this scenario. Since the shot-to-shot fluctuations are of random nature, a compensation effect can be observed, especially for higher laser shot numbers. Therefore, a fluctuation of ± 30% within the proton number does not translate into a dosimetric deviation of the same size. However, for plans with short delivery times these fluctuations cannot cancel out sufficiently, even for ± 10% fluctuations. Under the analyzed terms, it is feasible to achieve clinically relevant dose distributions with laser-driven proton beams. However, to keep the delivery times of the proton plans comparable to conventional proton plans for typical target volumes, a device is required which can modulate the bunch intensity from shot to shot. From the laser acceleration point of view, the proton number per bunch must be kept under control as well as the reproducibility of the bunches.

A treatment planning study to assess the feasibility of laser-driven proton therapy using a compact gantry design

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

Hofmann, Kerstin M., E-mail: kerstin.hofmann@lrz.tu-muenchen.de; Wilkens, Jan J.; Masood, Umar

Purpose: Laser-driven proton acceleration is suggested as a cost- and space-efficient alternative for future radiation therapy centers, although the properties of these beams are fairly different compared to conventionally accelerated proton beams. The laser-driven proton beam is extremely pulsed containing a very high proton number within ultrashort bunches at low bunch repetition rates of few Hz and the energy spectrum of the protons per bunch is very broad. Moreover, these laser accelerated bunches are subject to shot-to-shot fluctuations. Therefore, the aim of this study was to investigate the feasibility of a compact gantry design for laser-driven proton therapy and tomore » determine limitations to comply with. Methods: Based on a published gantry beam line design which can filter parabolic spectra from an exponentially decaying broad initial spectrum, a treatment planning study was performed on real patient data sets. All potential parabolic spectra were fed into a treatment planning system and numerous spot scanning proton plans were calculated. To investigate limitations in the fluence per bunch, the proton number of the initial spectrum and the beam width at patient entrance were varied. A scenario where only integer shots are delivered as well as an intensity modulation from shot to shot was studied. The resulting plans were evaluated depending on their dosimetric quality and in terms of required treatment time. In addition, the influence of random shot-to-shot fluctuations on the plan quality was analyzed. Results: The study showed that clinically relevant dose distributions can be produced with the system under investigation even with integer shots. For small target volumes receiving high doses per fraction, the initial proton number per bunch must remain between 1.4 × 10{sup 8} and 8.3 × 10{sup 9} to achieve acceptable delivery times as well as plan qualities. For larger target volumes and standard doses per fraction, the initial proton number is even more restricted to stay between 1.4 × 10{sup 9} and 2.9 × 10{sup 9}. The lowest delivery time that could be reached for such a case was 16 min for a 10 Hz system. When modulating the intensity from shot to shot, the delivery time can be reduced to 6 min for this scenario. Since the shot-to-shot fluctuations are of random nature, a compensation effect can be observed, especially for higher laser shot numbers. Therefore, a fluctuation of ±30% within the proton number does not translate into a dosimetric deviation of the same size. However, for plans with short delivery times these fluctuations cannot cancel out sufficiently, even for ±10% fluctuations. Conclusions: Under the analyzed terms, it is feasible to achieve clinically relevant dose distributions with laser-driven proton beams. However, to keep the delivery times of the proton plans comparable to conventional proton plans for typical target volumes, a device is required which can modulate the bunch intensity from shot to shot. From the laser acceleration point of view, the proton number per bunch must be kept under control as well as the reproducibility of the bunches.« less

Proton beam deflection in MRI fields: Implications for MRI-guided proton therapy.

PubMed

Oborn, B M; Dowdell, S; Metcalfe, P E; Crozier, S; Mohan, R; Keall, P J

2015-05-01

This paper investigates, via magnetic modeling and Monte Carlo simulation, the ability to deliver proton beams to the treatment zone inside a split-bore MRI-guided proton therapy system. Field maps from a split-bore 1 T MRI-Linac system are used as input to geant4 Monte Carlo simulations which model the trajectory of proton beams during their paths to the isocenter of the treatment area. Both inline (along the MRI bore) and perpendicular (through the split-bore gap) orientations are simulated. Monoenergetic parallel and diverging beams of energy 90, 195, and 300 MeV starting from 1.5 and 5 m above isocenter are modeled. A phase space file detailing a 2D calibration pattern is used to set the particle starting positions, and their spatial location as they cross isocenter is recorded. No beam scattering, collimation, or modulation of the proton beams is modeled. In the inline orientation, the radial symmetry of the solenoidal style fringe field acts to rotate the protons around the beam's central axis. For protons starting at 1.5 m from isocenter, this rotation is 19° (90 MeV) and 9.8° (300 MeV). A minor focusing toward the beam's central axis is also seen, but only significant, i.e., 2 mm shift at 150 mm off-axis, for 90 MeV protons. For the perpendicular orientation, the main MRI field and near fringe field act as the strongest to deflect the protons in a consistent direction. When starting from 1.5 m above isocenter shifts of 135 mm (90 MeV) and 65 mm (300 MeV) were observed. Further to this, off-axis protons are slightly deflected toward or away from the central axis in the direction perpendicular to the main deflection direction. This leads to a distortion of the phase space pattern, not just a shift. This distortion increases from zero at the central axis to 10 mm (90 MeV) and 5 mm (300 MeV) for a proton 150 mm off-axis. In both orientations, there is a small but subtle difference in the deflection and distortion pattern between protons fired parallel to the beam axis and those fired from a point source. This is indicative of the 3D spatially variant nature of the MRI fringe field. For the first time, accurate magnetic and Monte Carlo modeling have been used to assess the transport of generic proton beams toward a 1 T split-bore MRI. Significant rotation is observed in the inline orientation, while more complex deflection and distortion are seen in the perpendicular orientation. The results of this study suggest that due to the complexity and energy-dependent nature of the magnetic deflection and distortion, the pencil beam scanning method will be the only choice for delivering a therapeutic proton beam inside a potential MRI-guided proton therapy system in either the inline or perpendicular orientation. Further to this, significant correction strategies will be required to account for the MRI fringe fields.

Two Mechanisms Involved in Trigeminal CGRP Release: Implications for Migraine Treatment

PubMed Central

Durham, Paul L.; Masterson, Caleb G.

2012-01-01

Objective The goal of this study was to better understand the cellular mechanisms involved in proton stimulation of calcitonin gene-related peptide (CGRP) secretion from cultured trigeminal neurons by investigating the effects of two anti-migraine therapies, onabotulinumtoxin A and rizatriptan. Background Stimulated CGRP release from peripheral and central terminating processes of trigeminal ganglia neurons is implicated in migraine pathology by promoting inflammation and nociception. Based on models of migraine pathology, several inflammatory molecules including protons are thought to facilitate sensitization and activation of trigeminal nociceptive neurons and stimulate CGRP secretion. Despite the reported efficacy of triptans and onabotulinumtoxinA to treat acute and chronic migraine, respectively, a substantial number of migraneurs do not get adequate relief with these therapies. A possible explanation is that triptans and onabutulinumtoxinA are not able to block proton mediated CGRP secretion. Methods CGRP secretion from cultured primary trigeminal ganglia neurons was quantitated by radioimmunoassay while intracellular calcium and sodium levels were measured in neurons via live cell imaging using Fura2-AM and SBFI-AM, respectively. The expression of ASIC3 was determined by immunocytochemistry and western blot analysis. In addition, the involvement of ASICs in mediating proton stimulation of CGRP was investigated using the potent and selective ASIC3 inhibitor APETx2. Results While KCl caused a significant increase in CGRP secretion that was significantly repressed by treatment with EGTA, onabotulinumtoxinA, and rizatriptan, the stimulatory effect of protons (pH 5.5) was not suppressed by EGTA, onabotulinumtoxinA, or rizatriptan. In addition, while KCl caused a transient increase in intracellular calcium levels that was blocked by EGTA, no appreciable change in calcium levels was observed with proton treatment. However, protons did significantly increase the intracellular level of sodium ions. Under our culture conditions, ASIC3 was shown to be expressed in most trigeminal ganglion neurons. Importantly, proton stimulation of CGRP secretion was repressed by pretreatment with the ASIC3 inhibitor APETx2, but not the TRPV1 antagonist capsazepine. Conclusions Our findings provide evidence that proton regulated release of CGRP from trigeminal neurons utilizes a different mechanism than the calcium and SNAP-25 dependent pathways that are inhibited by the anti-migraine therapies rizatriptan and onabotulinumtoxinA. PMID:23095108

SU-F-T-666: Molecular-Targeted Gold Nanorods Enhances the RBE of Proton Therapy

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

Khoo, A; Sahoo, N; Krishnan, S

2016-06-15

Purpose: In recent years, proton beam radiation therapy (PBRT) has gained significant attention in the treatment of tumors in anatomically complex locations. However, the therapeutic benefit of PBRT is limited by a relative biological effectiveness (RBE) of just 1.1. The purpose of this study is to evaluate whether this limitation can be overcome by artificially enhancing the RBE using molecular-targeted gold nanorods (GNRs). Methods: Molecular-targeting of GNRs was accomplished using Cetuximab (antibody specific to epidermal growth factor receptor that is over-expressed in tumors) conjugated GNRs (cGNRs) and their binding affinity to Head and Neck cancer cells was confirmed using darkmore » field microscopy and Transmission Electron Microscopy (TEM). The radiosensitization potential of cGNRs when irradiated with photon (6MV) and proton (100 and 160 MeV) beams was determined using clonogenic assays. The RBE at 10% surviving fraction (RBE{sub 10}) for proton therapies at central and distal locations of SOBP was calculated with respect to 6 MV photons. IgGconjugated GNRs (iGNRs) were used as controls in all experiments. Results: cGNRs demonstrated significant radiosensitization when compared to iGNRs for 6MV photons (1.14 vs 1.04), 100 MeV protons (1.19 vs 1.04), and 160 MeV protons (1.17 vs 1.04). While RBE10 for proton beams at the center of SOBP revealed similar effects for both 100 and 160 MeV (RBE{sup 10}=1.39 vs 1.38; p>0.05), enhanced radiosensitization was observed at the distal SOBP with 100 MeV beams demonstrating greater effect than 160 MeV beams (RBE{sup 10}=1.79 vs 1.6; p<0.05). Conclusion: EGFR-targeting GNRs significantly enhance the RBE of protons well above the accepted 1.1 value. The enhanced RBE observed for lower energy protons (100 MeV) and at the distal SOBP suggests that low energy components may play a role in the observed radiosensitization effect. This strategy holds promise for clinical translation and could evolve as a paradigm-changing approach in the field of radiation oncology. The UT MD Anderson Cancer Center’s Institutional Research Grant funding to P. Diagaradjane.« less

Dosimetric characterization of a synthetic single crystal diamond detector in a clinical 62 MeV ocular therapy proton beam

NASA Astrophysics Data System (ADS)

Marinelli, Marco; Pompili, F.; Prestopino, G.; Verona, C.; Verona-Rinati, G.; Cirrone, G. A. P.; Cuttone, G.; La Rosa, R. M.; Raffaele, L.; Romano, F.; Tuvè, C.

2014-12-01

A synthetic single crystal diamond based Schottky photodiode was tested at INFN-LNS on the proton beam line (62 MeV) dedicated to the radiation treatment of ocular disease. The diamond detector response was studied in terms of pre-irradiation dose, linearity with dose and dose rate, and angular dependence. Depth dose curves were measured for the 62 MeV pristine proton beam and for three unmodulated range-shifted proton beams; furthermore, the spread-out Bragg peak was measured for a modulated therapeutic proton beam. Beam parameters, recommended by the ICRU report 78, were evaluated to analyze depth-dose curves from diamond detector. Measured dose distributions were compared with the corresponding dose distributions acquired with reference plane-parallel ionization chambers. Field size dependence of the output factor (dose per monitor unit) in a therapeutic modulated proton beam was measured with the diamond detector over the range of ocular proton therapy collimator diameters (5-30 mm). Output factors measured with the diamond detector were compared to the ones by a Markus ionization chamber, a Scanditronix Hi-p Si stereotactic diode and a radiochromic EBT2 film. Signal stability within 0.5% was demonstrated for the diamond detector with no need of any pre-irradiation dose. Dose and dose rate dependence of the diamond response was measured: deviations from linearity resulted to be within ±0.5% over the investigated ranges of 0.5-40.0 Gy and 0.3-30.0 Gy/min respectively. Output factors from diamond detector measured with the smallest collimator (5 mm in diameter) showed a maximum deviation of about 3% with respect to the high resolution radiochromic EBT2 film. Depth-dose curves measured by diamond for unmodulated and modulated beams were in good agreement with those from the reference plane-parallel Markus chamber, with relative differences lower than ±1% in peak-to-plateau ratios, well within experimental uncertainties. A 2.5% variation in diamond detector response was observed in angular dependence measurements carried-out by varying the proton beam incidence angle in the polar direction. The dosimetric characterization of the tested synthetic single crystal diamond detector clearly indicates its suitability for relative dosimetry in ocular therapy proton beams, with no need of any correction factors accounting for dose rate and linear energy transfer dependence.

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.

A Proton Beam Therapy System Dedicated to Spot-Scanning Increases Accuracy with Moving Tumors by Real-Time Imaging and Gating and Reduces Equipment Size

PubMed Central

Shimizu, Shinichi; Miyamoto, Naoki; Matsuura, Taeko; Fujii, Yusuke; Umezawa, Masumi; Umegaki, Kikuo; Hiramoto, Kazuo; Shirato, Hiroki

2014-01-01

Purpose A proton beam therapy (PBT) system has been designed which dedicates to spot-scanning and has a gating function employing the fluoroscopy-based real-time-imaging of internal fiducial markers near tumors. The dose distribution and treatment time of the newly designed real-time-image gated, spot-scanning proton beam therapy (RGPT) were compared with free-breathing spot-scanning proton beam therapy (FBPT) in a simulation. Materials and Methods In-house simulation tools and treatment planning system VQA (Hitachi, Ltd., Japan) were used for estimating the dose distribution and treatment time. Simulations were performed for 48 motion parameters (including 8 respiratory patterns and 6 initial breathing timings) on CT data from two patients, A and B, with hepatocellular carcinoma and with clinical target volumes 14.6 cc and 63.1 cc. The respiratory patterns were derived from the actual trajectory of internal fiducial markers taken in X-ray real-time tumor-tracking radiotherapy (RTRT). Results With FBPT, 9/48 motion parameters achieved the criteria of successful delivery for patient A and 0/48 for B. With RGPT 48/48 and 42/48 achieved the criteria. Compared with FBPT, the mean liver dose was smaller with RGPT with statistical significance (p<0.001); it decreased from 27% to 13% and 28% to 23% of the prescribed doses for patients A and B, respectively. The relative lengthening of treatment time to administer 3 Gy (RBE) was estimated to be 1.22 (RGPT/FBPT: 138 s/113 s) and 1.72 (207 s/120 s) for patients A and B, respectively. Conclusions This simulation study demonstrated that the RGPT was able to improve the dose distribution markedly for moving tumors without very large treatment time extension. The proton beam therapy system dedicated to spot-scanning with a gating function for real-time imaging increases accuracy with moving tumors and reduces the physical size, and subsequently the cost of the equipment as well as of the building housing the equipment. PMID:24747601

SU-E-T-764: Track Repeating Algorithm for Proton Therapy Applied to Intensity Modulated Proton Therapy for Head-And-Neck Patients

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

Yepes, P; Mirkovic, D; Mohan, R

Purpose: To determine the suitability of fast Monte Carlo techniques for dose calculation in particle therapy based on track-repeating algorithm for Intensity Modulated Proton Therapy, IMPT. The application of this technique will make possible detailed retrospective studies of large cohort of patients, which may lead to a better determination of Relative Biological Effects from the analysis of patient data. Methods: A cohort of six head-and-neck patients treated at the University of Texas MD Anderson Cancer Center with IMPT were utilized. The dose distributions were calculated with the standard Treatment Plan System, TPS, MCNPX, GEANT4 and FDC, a fast track-repeating algorithmmore » for proton therapy for the verification and the patient plans. FDC is based on a GEANT4 database of trajectories of protons in a water. The obtained dose distributions were compared to each other utilizing the g-index criteria for 3mm-3% and 2mm-2%, for the maximum spatial and dose differences. The γ-index was calculated for voxels with a dose at least 10% of the maximum delivered dose. Dose Volume Histograms are also calculated for the various dose distributions. Results: Good agreement between GEANT4 and FDC is found with less than 1% of the voxels with a γ-index larger than 1 for 2 mm-2%. The agreement between MCNPX with FDC is within the requirements of clinical standards, even though it is slightly worse than the comparison with GEANT4.The comparison with TPS yielded larger differences, what is also to be expected because pencil beam algorithm do not always performed well in highly inhomogeneous areas like head-and-neck. Conclusion: The good agreement between a track-repeating algorithm and a full Monte Carlo for a large cohort of patients and a challenging, site like head-and-neck, opens the path to systematic and detailed studies of large cohorts, which may yield better understanding of biological effects.« less