Therapy Facility Research Articles

The Next Ion Medical Machine Study at CERN: Towards a Next Generation Cancer Research and Therapy Facility with Ion Beams

The Next Ion Medical Machine Study at CERN: Towards a Next Generation Cancer Research and Therapy Facility with Ion Beams

Implementation of fulfillment of rehabilitation rights against persons with disabilities yayasan peduli kemanusiaan bali related to COVID-19: Human rights perspective

Fulfillment of the rights of persons with disabilities can be implemented by the government and society through non-profit organizations, one of which is the Bali Humanitarian Care Foundation (YPK). YPK is one of the rehabilitation center foundations in Bali, the activities are carried out quite regularly. This type of research is empirical legal research. The data collected was obtained through interviews, observation and documentation at YPK (persons with physical disabilities. Data analysis techniques used qualitative methods. In early 2019 the world faced COVID-19 which caused various orders to undergo significant changes. Governor of Bali Number 46 of 2020 concerning health protocols up to Governor Circular Number 01 of 2021 concerning Restriction of Community Activities in dealing with COVID-19 which causes interaction patterns to change. The purpose of this study is to analyze the obstacles and solutions that occur in fulfilling the right to rehabilitation for persons with disabilities. There needs to be social attention that can be done in community participation, such as the types of fundraising to help rehabilitation therapy facilities and facilities.

Resilience will buy biologics maker Ology

National Resilience, a venture-backed pharmaceutical services company formed last year, will acquire Ology Bioservices, a maker of active ingredients for biologic drugs, in Alachua, Florida. Resilience, which targets the development of manufacturing processes for advanced drugs, previously acquired Therapure Biopharma in Ontario and a former Genzyme plant in Boston. It also recently subleased an Orchard Therapeutics gene therapy facility in Fremont, California.

Community aquatic therapy for Parkinson’s disease: an international qualitative study

Purpose To explore the opinions of people living with Parkinson’s disease about access to and participation in community aquatic therapy. Methods Focus groups and individual interviews were conducted with people living with Parkinson’s disease in Ireland (n = 24) and Australia (n = 10). All discussions were audio-recorded, transcribed verbatim, and thematically analysed. Results Four main themes were identified. Primarily, participants were optimistic about their reasons for choosing aquatic therapy and found it beneficial to their health and well-being. Optimal components of aquatic therapy identified were access to individually tailored aquatic programs, completed as a minimum once a week, at a moderate to high-intensity level, and guided by a credentialed instructor. Fear was a significant barrier for a small proportion of participants and was linked to water competence, past experiences, and fall risk associated with the aquatic environment. Participants identified a strong need for education and increased awareness about aquatic therapy benefits to promote greater engagement. Conclusion Aquatic therapy is a popular exercise choice for people with Parkinson’s disease, especially in the early to middle disease stages. Considering the views of people living with Parkinson’s disease can aid the design and implementation of interventions and future aquatic research internationally. Implications for Rehabilitation Aquatic therapy is emerging as an effective physiotherapy approach for managing motor and non-motor symptoms in Parkinson’s disease. Little is known regarding community-based aquatic therapy programs from the perspectives of people living with Parkinson’s disease internationally. People with Parkinson’s disease may benefit from timely information about the unique benefits, prerequisites, and local aquatic therapy facilities to promote greater uptake of aquatic programs. Tailored aquatic therapy interventions delivered within a group setting by a credentialed healthcare professional may increase long-term adherence.

Physical characterization of 3He ion beams for radiotherapy and comparison with 4He

There is increasing interest in using helium ions for radiotherapy, complementary to protons and carbon ions. A large number of patients were treated with 4He ions in the US heavy ion therapy project and novel 4He ion treatment programs are under preparation, for instance in Germany and Japan. 3He ions have been proposed as an alternative to 4He ions because the acceleration of 3He is technically less difficult than 4He. In particular, beam contaminations have been pointed out as a potential safety issue for 4He ion beams. This motivated a series of experiments with 3He ion beams at Gesellschaft für Schwerionenforschung (GSI), Darmstadt. Measured 3He Bragg curves and fragmentation data in water are presented in this work. Those experimental data are compared with FLUKA Monte Carlo simulations. The physical characteristics of 3He ion beams are compared to those of 4He, for which a large set of data became available in recent years from the preparation work at the Heidelberger Ionenstrahl-Therapiezentrum (HIT). The dose distributions (spread out Bragg peaks, lateral profiles) that can be achieved with 3He ions are found to be competitive to 4He dose distributions. The effect of beam contaminations on 4He depth dose distribution is also addressed. It is concluded that 3He ions can be a viable alternative to 4He, especially for future compact therapy accelerator designs and upgrades of existing ion therapy facilities.

Proton linac-based therapy facility for ultra-high dose rate (FLASH) treatment

As an advanced treatment method in the past five years, ultra-high dose rate (FLASH) radiotherapy as a breakthrough and milestone in radiotherapy development has been verified to be much less harmful to healthy tissues in different experiments. FLASH treatments require an instantaneous dose rate as high as hundreds of grays per second to complete the treatment in less than 100 ms. Current proton therapy facilities with the spread-out of the Bragg peak formed by different energy layers, to our knowledge, cannot easily achieve an adequate dose rate for FLASH treatments because the energy layer switch or gantry rotation of current facilities requires a few seconds, which is relatively long. A new design for a therapy facility based on a proton linear accelerator (linac) for FLASH treatment is proposed herein. It is designed under two criteria: no mechanical motion and no magnetic field variation. The new therapy facility can achieve an ultra-high dose rate of up to 300 Gy/s; however, it delivers an instantaneous dose of 30 Gy within 100 ms to complete a typical FLASH treatment. The design includes a compact proton linac with permanent magnets, a fast beam kicker in both azimuth and elevation angles, a fixed gantry with a static superconducting coil to steer proton bunches with all energy, a fast beam scanner using radio-frequency (RF) deflectors, and a fast low-level RF system. All relevant principles and conceptual proposals are presented herein.

Design, fabrication, and cold test of an S-band high-gradient accelerating structure for compact proton therapy facility

An S-band high-gradient accelerating structure is designed for a proton therapy linear accelerator (linac) to accommodate the new development of compact, single-room facilities and ultra-high dose rate (FLASH) radiotherapy. To optimize the design, an efficient optimization scheme is applied to improve the simulation efficiency. An S-band accelerating structure with 2856 MHz is designed with a low beta of 0.38, which is a difficult structure to achieve for a linac accelerating proton particles from 70 to 250 MeV, as a high gradient up to 50 MV/m is required. A special design involving a dual-feed coupler eliminates the dipole field effect. This paper presents all the details pertaining to the design, fabrication, and cold test results of the S-band high-gradient accelerating structure.

Secondary and activated X($$\gamma$$) radiation of SPHIC particle therapy facility

We report the secondary X( $$\gamma$$ ) radiation from the accelerator in a normal operating state and activated X( $$\gamma$$ ) radiation from the accelerator devices when the accelerator stops operating in the cancer treatment facility of the Shanghai Proton and Heavy Ion Center (SPHIC). These radiation measurements show us the structural radiation distribution along the beam lines and devices inside the accelerator room when the beam is on and off and can support the radiation protection design of the accelerator facility used for cancer treatment and help evaluate the accumulated radiation dose in the case of an emergency, such as a personal safety system failure or a radiation accident. The radiation dose rate measured in this facility shows that the facility is safe from the radiation protection point. After shooting the quality assurance (QA) beam, the radiation dose rate in the treatment room was also measured to investigate the radiation dose space distribution and decay time dependence. In addition, the time period before safely entering the treatment room after determining the shooting of the QA beam is recommended to be approximately 5 min.

Animal tissue-based quantitative comparison of dual-energy CT to SPR conversion methods using high-resolution gel dosimetry

Dual-energy computed tomography (DECT) has been shown to allow for more accurate ion therapy treatment planning by improving the estimation of tissue stopping power ratio (SPR) relative to water, among other tissue properties. In this study, we measured and compared the accuracy of SPR values derived using both dual- and single-energy CT (SECT) based on different published conversion algorithms. For this purpose, a phantom setup containing either fresh animal soft tissue samples (beef, pork) and a water reference or tissue equivalent plastic materials was designed and irradiated in a clinical proton therapy facility. Dosimetric polymer gel was positioned downstream of the samples to obtain a three-dimensional proton range distribution with high spatial resolution. The mean proton range in gel for each tissue relative to the water sample was converted to a SPR value. Additionally, the homogeneous samples were probed with a variable water column encompassed by two ionization chambers to benchmark the SPR accuracy of the gel dosimetry. The SPR values measured with both methods were consistent with a mean deviation of 0.2%, but the gel dosimetry captured range variations up to 5 mm within individual samples.Across all fresh tissue samples the SECT approach yielded significantly greater mean absolute deviations from the SPR deduced using gel range measurements, with an average difference of 1.2%, compared to just 0.3% for the most accurate DECT-based algorithm. These results show a significant advantage of DECT over SECT for stopping power prediction in a realistic setting, and for the first time allow to compare a large set of methods under the same conditions.

Long Turnaround Times in Viral Load Monitoring of People Living with HIV in Resource-Limited Settings.

Introduction:Routine viral load (VL) testing is fraught with challenges in resource-limited settings which lead to longer turnaround times for the return of VL results. We assessed the turnaround times for VL testing and factors associated with long turnaround (>30 days) in Marondera, Zimbabwe, between January and September 2018.Methods:This was an analytical study of routine program data. Data were extracted from electronic records and paper-based reports at two laboratories and at antiretroviral therapy (ART) facilities. The unit of analysis was the VL sample. Duration (in days) between sample collection and sample testing (pre-test turnaround time), duration between sample testing and receipt of VL result at ART the site (post-test turnaround time), and duration between sample collection and receipt of result at the ART site (overall turnaround time) were calculated. Days on which the VL testing machine was not functional, and workload (number of tests done per month) were used to assess associations. We used binomial log models to assess the factors associated with longer turnaround time.Results:A total of 3348 samples were received at the two VL testing laboratories, and 3313 were tested, of these, 1111 were analyzed for overall turnaround time. Pre-test, post-test, and overall turnaround times were 22 days (interquartile range (IQR): 11–41), 51 days (IQR: 30–89), and 67 days (IQR: 46–100), respectively. Laboratory workload (relative risk [RR]: 1.12, 95% confidence interval [CI]: 1.10–1.14) and machine break down (RR: 1.15, 95% CI: 1.14–1.17) were associated with long turnaround time.Conclusions:Routine VL turnaround time was long. Decentralizing VL testing and enhancing laboratory capacity may help shorten the turnaround time.

Results of an independent dosimetry audit for scanned proton beam therapy facilities

PurposeAn independent dosimetry audit based on end-to-end testing of the entire chain of radiation therapy delivery is highly recommended to ensure consistent treatments among proton therapy centers. This study presents an auditing methodology developed by the MedAustron Ion Beam Therapy Center (Austria) in collaboration with the National Physical Laboratory (UK) and audit results for five scanned proton beam therapy facilities in Europe. MethodsThe audit procedure used a homogeneous and an anthropomorphic head phantom. The phantoms were loaded either with an ionization chamber or with alanine pellets and radiochromic films. Homogeneously planned doses of 10Gy were delivered to a box-like target volume in the homogeneous phantom and to two clinical scenarios with increasing complexity in the head phantom. ResultsFor all tests the mean of the local differences of the absolute dose to water determined with the alanine pellets compared to the predicted dose from the treatment planning system installed at the audited institution was determined. The mean value taken over all tests performed was −0.1±1.0%. The measurements carried out with the ionization chamber were consistent with the dose determined by the alanine pellets with a mean deviation of −0.5±0.6%. ConclusionThe developed dosimetry audit method was successfully applied at five proton centers including various “turn-key” Cyclotron solutions by IBA, Varian and Mevion. This independent audit with extension to other tumour sites and use of the correspondent anthropomorphic phantoms may be proposed as part of a credentialing procedure for future clinical trials in proton beam therapy.

Prototype development of the beam diagnostic system of a proton therapy facility based on a superconducting cyclotron

A proton therapy facility (HUST-PTF) based on a 250 MeV isochronous superconducting cyclotron is under construction in the Huazhong University of Science and Technology. An energy degrader is used to modulate the beam energy from 70 to 230 MeV in HUST-PTF, and then transports the proton beams to one fixed-beamline room and two gantry rooms for clinical treatments. As a compromise between the cost and effectiveness of the beam diagnostic system, three kinds of commonly used detectors, scintillation screen, ionization chamber and Faraday cup are adopted to measure the proton beam profile, position and intensity in the HUST-PTF beamline. Here we introduce the latest progress on the development of the beam diagnostic system of the HUST-PTF beamline, including the physical, mechanical and control issues, as well as some test results of the front-end electronics.

FLASH Irradiation with Proton Beams: Beam Characteristics and Their Implications for Beam Diagnostics

FLASH irradiations use dose-rates orders of magnitude higher than commonly used in patient treatments. Such irradiations have shown interesting normal tissue sparing in cell and animal experiments, and, as such, their potential application to clinical practice is being investigated. Clinical accelerators used in proton therapy facilities can potentially provide FLASH beams; therefore, the topic is of high interest in this field. However, a clear FLASH effect has so far been observed in presence of high dose rates (>40 Gy/s), high delivered dose (tens of Gy), and very short irradiation times (<300 ms). Fulfilling these requirements poses a serious challenge to the beam diagnostics system of clinical facilities. We will review the status and proposed solutions, from the point of view of the beam definitions for FLASH and their implications for beam diagnostics. We will devote particular attention to the topics of beam monitoring and control, as well as absolute dose measurements, since finding viable solutions in these two aspects will be of utmost importance to guarantee that the technique can be adopted quickly and safely in clinical practice.

Dead time corrections for Bonner sphere measurements of secondary neutrons at a proton therapy facility

Radiation therapy with proton beams allows the deposition of high doses to the tumour while minimising dose to the surrounding tissue. During such treatment, the patient is also exposed to secondary radiation which produces an out-of-field dose that affects healthy tissue. The largest contribution to this out-of-field dose comes from neutron radiation; therefore, it is of interest to fully characterise the neutron field in the therapy room with measurements. This is usually done with Bonner sphere spectrometers using active detectors, typically 3He-filled proportional counters, as central thermal neutron sensors. Under the experimental conditions encountered in proton therapy facilities, a proper analysis of the measurements is impossible unless dead time corrections are implemented. In this paper, we present a method using a paralysable dead time model for carrying out such corrections for Bonner sphere measurements with 3He-filled proportional counters and apply it to data taken at the University Proton Therapy Dresden (UPTD) facility in double scattering mode. The neutron events were recorded with time stamps and, based on this time-resolved data, the measured neutron rate distribution was sampled. Since the neutron flux is proportional to the proton flux, the integral neutron flux is directly related to the proton dose. Hence, we were able to estimate the detector dead time from the measured rate distributions recorded for a set of measurements with different proton dose rates. Experimental measurements with different intensities of the proton field show that the corrections are in agreement within 0.5% for measured signal rates smaller than 15 × 103 counts per second and do not exceed 1% at 25 × 103 counts per second.

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities.

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

A comprehensive Monte Carlo study of out-of-field secondary neutron spectra in a scanned-beam proton therapy gantry room

PurposeTo simulate secondary neutron radiation fields that had been measured at different relative positions during phantom irradiation inside a scanning proton therapy gantry treatment room. Further, to identify origin, energy distribution, and angular emission of the secondary neutrons as a function of proton beam energy. MethodsThe FLUKA Monte Carlo code was used to model the relevant parts of the treatment room in a scanned pencil beam proton therapy gantry including shielding walls, floor, major metallic gantry-components, patient table, and a 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° and 135° relative to the beam axis at 2m distance from isocenter for monoenergetic 11×11cm2 fields from 200MeV, 140MeV, 75MeV initial proton beams, as well as for 118MeV protons with a 5cm thick PMMA range shifter. The total neutron spectra were scored for these four positions and proton energies. FLUKA neutron spectra simulations were crosschecked with Geant4 simulations using initial proton beam properties from FLUKA-generated phase spaces. Additionally, the room-components generating secondary neutrons in the room and their contributions to the total spectrum were identified and quantified. ResultsFLUKA and Geant4 simulated neutron spectra showed good general agreement with published measurements in the whole simulated neutron energy range of 10−10 to 103MeV. As in previous studies, high-energy (E≥19.6MeV) neutrons from the phantom are most prevalent along 0°, while thermalized (1meV≤E<0.4eV) and fast (100keV≤E<19.4MeV) neutrons dominate the spectra in the lateral and backscatter direction. The iron of the large bending magnet and its counterweight mounted on the gantry were identified as the most determinant sources of secondary fast-neutrons, which have been lacking in simplified room simulations. ConclusionsThe results helped disentangle the origin of secondary neutrons and their dominant contributions and were strengthened by the fact that a cross comparison was made using two independent Monte Carlo codes. The complexity of such room model can in future be limited using the result. They may further be generalized in that they can be used for an assessment of neutron fields, possibly even at facilities where detailed neutron measurements and simulations cannot be performed. They may also help to design future proton therapy facilities and to reduce unwanted radiation doses from secondary neutrons to patients.

Optimization of a B[formula omitted]C/graphite composite energy degrader and its shielding for a proton therapy facility

Proton therapy is an advanced cancer treatment modality due to its ability to precisely deliver radiation doses to tumors using the Bragg peak effect. An energy degrader plays a vital role at a cyclotron-based proton therapy facility, as it provides a rapid, reliable, and reproducible method of setting the appropriate beam energy for radiotherapy. However, the protons undergo nuclear interactions with the matter in the degrader, leading to significant secondary particles causing a large ambient radiation dose nearby, creating severe risks for the facility operation. This study investigated the beam loss mechanism and the secondary particle generation in a B4C/graphite composite (BGC) energy degrader. Monte Carlo simulations were performed to ensure the shielding design’s reliability. Calculations showed that the BGC degrader had a higher beam transmission efficiency than a pure graphite degrader, while the secondary neutron yield was higher. An optimum shielding configuration can significantly reduce the radiation dose to an acceptable level for sensitive devices and maintenance staff.

Development and characterization of optical readout well-type glass gas electron multiplier for dose imaging in clinical carbon beams.

The use of carbon ion beams in cancer therapy (also known as hadron therapy) is steadily growing worldwide; therefore, the demand for more efficient dosimetry systems is also increasing because daily quality assurance (QA) measurements of hadron radiotherapy is one of the most complex and time consuming tasks. The aim of this study is to develop a two-dimensional dosimetry system that offers high spatial resolution, a large field of view, quick data response, and a linear dose-response relationship. We demonstrate the dose imaging performance of a novel digital dose imager using carbon ion beams for hadron therapy. The dose imager is based on a newly-developed gaseous detector, a well-type glass gas electron multiplier. The imager is successfully operated in a hadron therapy facility with clinical intensity beams for radiotherapy. It features a high spatial resolution of less than 1mm and an almost linear dose-response relationship with no saturation and very low linear-energy-transfer dependence. Experimental results show that the dose imager has the potential to improve dosimetry accuracy for daily QA.

Out-of-field doses for scanning proton radiotherapy of shallowly located paediatric tumours—a comparison of range shifter and 3D printed compensator

The lowest possible energy of proton scanning beam in cyclotron proton therapy facilities is typically between 60 and 100 MeV. Treatment of superficial lesions requires a pre-absorber to deliver doses to shallower volumes. In most of the cases a range shifter (RS) is used, but as an alternative solution, a patient-specific 3D printed proton beam compensator (BC) can be applied. A BC enables further reduction of the air gap and consequently reduction of beam scattering. Such pre-absorbers are additional sources of secondary radiation. The aim of this work was the comparison of RS and BC with respect to out-of-field doses for a simulated treatment of superficial paediatric brain tumours. EURADOS WG9 performed comparative measurements of scattered radiation in the Proteus C-235 IBA facility (Cyclotron Centre Bronowice at the Institute of Nuclear Physics, CCB IFJ PAN, Kraków, Poland) using two anthropomorphic phantoms—5 and 10 yr old—for a superficial target in the brain. Both active detectors located inside the therapy room, and passive detectors placed inside the phantoms were used. Measurements were supplemented by Monte Carlo simulation of the radiation transport. For the applied 3D printed pre-absorbers, out-of-field doses from both secondary photons and neutrons were lower than for RS. Measurements with active environmental dosimeters at five positions inside the therapy room indicated that the RS/BC ratio of the out-of-field dose was also higher than one, with a maximum of 1.7. Photon dose inside phantoms leads to higher out-of-field doses for RS than BC to almost all organs with the highest RS/BC ratio 12.5 and 13.2 for breasts for 5 and 10 yr old phantoms, respectively. For organs closest to the isocentre such as the thyroid, neutron doses were lower for BC than RS due to neutrons moderation in the target volume, but for more distant organs like bladder—conversely—lower doses for RS than BC were observed. The use of 3D printed BC as the pre-absorber placed in the near vicinity of patient in the treatment of superficial tumours does not result in the increase of secondary radiation compared to the treatment with RS, placed far from the patient.

Commissioning of GPU–Accelerated Monte Carlo Code FRED for Clinical Applications in Proton Therapy

We present commissioning and validation of Fred, a graphical processing unit (GPU)–accelerated Monte Carlo code, for two proton beam therapy facilities of different beam line design: CCB (Krakow, IBA) and EMORY (Atlanta, Varian). We followed clinical acceptance tests required to approve the certified treatment planning system for clinical use. We implemented an automated and efficient procedure to build a parameter library characterizing the clinical proton pencil beam. Beam energy, energy spread, lateral propagation model, and a dosimetric calibration factor were parametrized based on measurements performed during the facility start-up. The Fred beam model was validated against commissioning and supplementary measurements performed with and without range shifter. We obtained 1) submillimeter agreement of Bragg peak shapes in water and lateral beam profiles in air and slab phantoms, 2) &lt;2% dose agreement for spread out Bragg peaks of different ranges, 3) average gamma index (2%/2 mm) passing rate of &gt;95% for &gt;1000 patient verification measurements using a two-dimensional array of ionization chambers, and 4) gamma index passing rate of &gt;99% for three-dimensional dose distributions computed with Fred and measured with an array of ionization chambers behind an anthropomorphic phantom. The results of example treatment planning study on &gt;100 patients demonstrated that Fred simulations in computed tomography enable an accurate prediction of dose distribution in patient and application of Fred as second patient quality assurance tool. Computation of a patient treatment in a CT using 104 protons per pencil beam took on average 2′30 min with a tracking rate of 2.9×105p+/s. Fred was successfully commissioned and validated against the clinical beam model, showing that it could potentially be used in clinical routine. Thanks to high computational performance due to GPU acceleration and an automated beam model implementation method, the application of Fred is now possible for research or quality assurance purposes in most of the proton facilities.