Magnetic resonance linear accelerator technology and adaptive radiation therapy: An overview for clinicians.

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART.

Asia-Pacific Special Interest Group: The first ten years.

INTRODUCTION: The Asia-Pacific Special Interest Group (APSIG) was formed in 2009 by the Australian College of Physical Scientists and Engineers in Medicine (ACPSEM) to support radiation oncology services in low-to-middle income countries in our region. In 2017, APSIG moved to the ACPSEM's charity, the Better Healthcare Technology (BHT) Foundation, enabling improvement in fundraising, marketing and partnerships with like-minded organizations. METHODS: APSIG's main activity is to recruit certified medical physicists as volunteers to train local staff in countries such as Vietnam, Cambodia, Myanmar and Mongolia. APSIG also supports remote mentoring, coordinates the delivery of donated radiotherapy equipment, and brings Asia-Pacific medical physicists to Australia and New Zealand for conferences and hospital training. RESULTS: The number of APSIG volunteer assignments has been steadily increasing over the last decade. Challenges include the limited number of ACPSEM certified medical physics volunteers, the limited opportunities to train the local physicists due to their heavy workloads, and language barriers. The COVID-19 pandemic has halted volunteer assignments for now but a range of alternative means of assistance such as webinars, online tutorials and virtual meetings are planned to continue APSIG's activities. CONCLUSION: APSIG will continue to provide a support service to radiation oncology staff in the Asia-Pacific region. APSIG and the BHT Foundation's work promotes quality health care by supporting medical physicists in Asia-Pacific countries and championing better radiotherapy technology access and treatment knowledge sharing.

Establishment of Microbeam Radiation Therapy at a Small-Animal Irradiator.

PURPOSE: Microbeam radiation therapy is a preclinical concept in radiation oncology. It spares normal tissue more effectively than conventional radiation therapy at equal tumor control. The radiation field consists of peak regions with doses of several hundred gray, whereas doses between the peaks (valleys) are below the tissue tolerance level. Widths and distances of the beams are in the submillimeter range for microbeam radiation therapy. A similar alternative concept with beam widths and distances in the millimeter range is presented by minibeam radiation therapy. Although both methods were developed at large synchrotron facilities, compact alternative sources have been proposed recently. METHODS AND MATERIALS: A small-animal irradiator was fitted with a special 3-layered collimator that is used for preclinical research and produces microbeams of flexible width of up to 100 µm. Film dosimetry provided measurements of the dose distributions and was compared with Monte Carlo dose predictions. Moreover, the micronucleus assay in Chinese hamster CHO-K1 cells was used as a biological dosimeter. The focal spot size and beam emission angle of the x-ray tube were modified to optimize peak dose rate, peak-to-valley dose ratio (PVDR), beam shape, and field homogeneity. An equivalent collimator with slit widths of up to 500 µm produced minibeams and allowed for comparison of microbeam and minibeam field characteristics. RESULTS: The setup achieved peak entrance dose rates of 8 Gy/min and PVDRs >30 for microbeams. Agreement between Monte Carlo simulations and film dosimetry is generally better for larger beam widths; qualitative measurements validated Monte Carlo predicted results. A smaller focal spot enhances PVDRs and reduces beam penumbras but substantially reduces the dose rate. A reduction of the beam emission angle improves the PVDR, beam penumbras, and dose rate without impairing field homogeneity. Minibeams showed similar field characteristics compared with microbeams at the same ratio of beam width and distance but had better agreement with simulations. CONCLUSION: The developed setup is already in use for in vitro experiments and soon for in vivo irradiations. Deviations between Monte Carlo simulations and film dosimetry are attributed to scattering at the collimator surface and manufacturing inaccuracies and are a matter of ongoing research.

Radiotherapy activities and technological equipment in Veneto, Italy: a report from the Rete Radioterapica Veneta.

BACKGROUND: Despite the pivotal role of radiotherapy in oncology, the provision of radiation treatments remains inadequate in many areas of the world. The present report is an assessment conducted among Radiation Oncology centers of Veneto region with the aim to collect information concerning radiotherapy assets and technological equipment availability. METHODS: Data concerning Veneto Radiation Oncology departments about radiotherapy activities, number of treatments, techniques used and radiotherapy machines available were collected. The reference time period was 2018. Reimbursement system databases and business intelligence systems were used. Extra-regional attraction and migration were evaluated. When available, data were compared to previous years. RESULTS: Veneto in 2018 was endowed with 1 megavolt unit for about 153,000 inhabitants. The number of megavolt machines per million inhabitants resulted to be 6.72. In 51% of radiotherapy treatments, intensity-modulated techniques were performed. Six percent of treatments were administered to extra-regional patients. CONCLUSION: Radiotherapy assets and equipment in Veneto seem to be appropriate to standard requests in terms of availability and technology.

IRIDIUM-192 RADIOTHERAPY BENEFITS IN THE MANAGEMENT OF GYNECOLOGICAL TUMORS. / PEREVAGY IONIZUIuChOGO VYPROMINIuVANNIa IRYDIIu-192 U PROMENEVOMU LIKUVANNI ONKOGINEKOLOGIChNYKh ZAKhVORIuVAN'.

BACKGROUND: Application of the most advanced radiation technologies of brachytherapy featuring the high dose ratesources i.e. 60Co and 192Ir within contemporary management protocols for gynecological cancer provides maximum dosedistribution in the clinical target along with minimal radiation exposure on surrounding organs and tissues. It involvesirradiation of large spaces with delivery of high therapeutic doses at the tolerance bound of «critical¼ organs (bladder,rectum) and tissues. Thus minimization of the early and late radiation complications, life span extent and quality oflife increase remain just the issues in contemporary radiation oncology requiring therefore the elaboration of radiobiological criteria along with substantiation of physiсо-engineering properties of the radiation sources. Taking intoaccount the basic radiobiological patterns will ensure a definitive further progress in the field of radiation oncology. OBJECTIVE: to study and compare the biological effects of 192Ir with the effects of the reference gamma radiation 60Coand increase the effectiveness of brachytherapy using a 192Ir source. MATERIALS AND METHODS: Radiobiological dosimetry on the basis of a test system of peripheral blood lymphocytesfrom the gynecological cancer patients with subsequent cytogenetic analysis of radiation-induced chromosomeaberrations was performed to study and compare the biological effects of 192Ir and reference 60Со γ-radiation, and toenhance the efficiency of 192Ir brachytherapy. RESULTS: Radiation markers, i.e. dicentric chromosomes with an accompanying paired fragment prevailed in thespectrum of radiation-induced damage. Variability of individual cytogenetic parameters of peripheral lymphocytesupon the first fraction of irradiation at the same dose of 5 Gy indicated an individual sensitivity of patients to the192Ir γ-irradiation. Comprehensive conservative treatment with adjuvant radiotherapy was applied to the patients(n = 98) having got secondary vaginal cancer stage II-III, T2-3N0-1M0. The high dose-rate (HDR) brachytherapy using 192Ir radiation sources was applied in the main study group (n = 37), HDR brachytherapy using 60Co radiation sourceswas applied in the control group (n = 35). CONCLUSION: The HDR brachytherapy with 192Ir and 60Co sources on the up-to-date technology intensive devices provides a high accuracy of dose distributions when irradiating the malignant neoplasms with minimized radiationexposure to the «critical¼ tissues. Treatment results are improved therefore. The use of 192Ir radiation sources compared with 60Co ones resulted in an increased throughput of treatment, enhanced tumor regression, and reduced incidence of radiation effects on the critical organs. Currently we perform the radiobiological studies on somatic cellsfrom cancer patients at the genetic, biochemical, biophysical, and cytological levels in order to receive a biologicalindication of radiation damage under the impact of 192Ir isotope. Continuation of clinical trials with radiobiologicalsupport will provide an opportunity to predict the early and late radiation complications and thus to provide a personalized approach in brachytherapy of cancer patients using the 192Ir sources of γ-rays.

Radiation Oncology in Oman: Current Status and Future Challenges.

Oman is a high-income Middle Eastern country. Over the past 50 years, the country's health care system has undergone revolutionary changes to meet the health care needs of its population, driven by high oil and gas revenues. It currently has a very efficient universal health care system. There are 2 linear accelerators in the country and 6 radiation oncologists. A new cancer research center is currently under construction. The major challenge that could affect the delivery of radiation therapy in the future is sustenance of the health care achievements in view of a growing population and the reliance on public funding for health care delivery.

How to work together between nuclear medicine and radiotherapy departments?

Among the available imaging techniques, functional imaging provided by nuclear medicine departments represents a tool of choice for the oncoradiotherapist for targeting tumour activity, with positron emission tomography as the main modality. Before, during or after radiotherapy, functional imaging helps guide the oncoradiotherapist in making decisions and in the strategic choice of pathology management. Setting up a working group to ensure perfect coordination at all levels is the first step. Key points for a common and coordinated management between the two departments are the definition of an organizational logistic, training of personnel at every levels, standardization of nomenclatures, the choice of adapted and common equipment, implementation of regulatory controls, and research/clinical routine continuum. The availability of functional examinations dedicated to radiotherapy in clinical routine is possible and requires a convergence of teams and a pooling of tools and techniques.

Realizing Clinical Trials with Astatine-211: The Chemistry Infrastructure.

Despite the consensus around the clinical potential of the α-emitting radionuclide astatine-211 (211At), there are only a limited number of research facilities that work with this nuclide. There are three main reasons for this: (1) Scarce availability of the nuclide. Despite a relatively large number of globally existing cyclotrons capable of producing 211At, few cyclotron facilities produce the nuclide on a regular basis. (2) Lack of a chemical infrastructure, that is, isolation of 211At from irradiated targets and the subsequent synthesis of an astatinated product. At present, the research groups that work with 211At depend on custom systems for recovering 211At from the irradiated targets. Setting up and implementing such custom units require long lead times to provide a proper working system. (3) The chemistry of 211At. Compared with radiometals there are no well-established and generally accepted synthesis methods for forming sufficiently stable bonds between 211At and the tumor-specific vector to allow for systemic applications. Herein we present an overview of the infrastructure of producing 211At radiopharmaceuticals, from target to radiolabeled product including chemical strategies to overcome hurdles for advancement into clinical trials with 211At.

An IAEA survey of radiotherapy practice including quality assurance extent and depth.

Background: The IAEA recommends a quality assurance program in radiotherapy to ensure safe and effective treatments. In this study, radiotherapy departments were surveyed on their current practice including the extent and depth of quality assurance activities.Methods: Radiotherapy departments were voluntarily surveyed in three stages, firstly, in basic facility information, secondly, in quality assurance activities and treatment techniques, and thirdly, in a snapshot of quality assurance, departmental and treatment activities.Results: The IAEA received completed surveys from 381 radiotherapy departments throughout the world with 100 radiotherapy departments completing all three surveys. Dominant patterns were found in linac-based radiotherapy with access to treatment planning systems for 3D-CRT and 3D imaging. Staffing levels for major staff groups were on average in the range recommended by the IAEA. The modal patient workload per EBRT unit was as expected in the range of 21-30 patients per day, however significant instances of high workload (more than 50 patients per day per treatment unit) were reported. Staffing levels were found to correlate with amount of treatment equipment and patient workload. In a self-assessment of quality assurance performance, most radiotherapy departments reported that they would perform at least 60% of the quality assurance activities itemized in the second survey, with particular strength in equipment quality control. In a snapshot survey of quality assurance performance, again equipment quality control practice was well developed, particularly for the treatment equipment.Conclusions: The IAEA surveys provide a snapshot of current radiotherapy practice including quality assurance activities.

Comparing medical grade to commercial grade display in a radiation oncology environment.

Electronic displays are used in every modern day medical clinic. They are used to view images that are needed to diagnose, treat, and follow-up on patients with a variety of conditions. The type of electronic display used varies from department to department. Currently, a type of displays called medical grade displays are used to evaluate and diagnose disease and conditions. Alternatively, commercial or entry level professional displays are used for almost everything else. In the field of radiation oncology medical images are often used to plan the treatment course for each patient. These images are always viewed using a commercial grade display. An experiment was completed to examine the role a medical grade display might have in a radiation oncology setting. Our study had certified dosimetrists and radiation oncologists view medical images on both a medical grade and commercial grade display and rank their preference on a scale. The observers assessed the images in different categories (Contrast, resolution, and sharpness) and also commented on their preference. Results indicated that the medical grade display performed better than the commercial grade display in every image quality category.

Master Protocol Trial Design for Efficient and Rational Evaluation of Novel Therapeutic Oncology Devices.

Historically, the gold standard for evaluation of cancer therapeutics, including medical devices, has been the randomized clinical trial. Although high-quality clinical data are essential for safe and judicious use of therapeutic oncology devices, class II devices require only preclinical data for US Food and Drug Administration approval and are often not rigorously evaluated prior to widespread uptake. Herein, we review master protocol design in medical oncology and its application to therapeutic oncology devices, using examples from radiation oncology. Unique challenges of clinical testing of radiation oncology devices (RODs) include patient and treatment heterogeneity, lack of funding for trials by industry and health-care payers, and operator dependence. To address these challenges, we propose the use of master protocols to optimize regulatory, financial, administrative, quality assurance, and statistical efficiency of trials evaluating RODs. These device-specific master protocols can be extrapolated to other devices and encompass multiple substudies with the same design, statistical considerations, logistics, and infrastructure. As a practical example, we outline our phase I and II master protocol trial of stereotactic magnetic resonance imaging-guided adaptive radiotherapy, which to the best of our knowledge is the first master protocol trial to test a ROD. Development of more efficient clinical trials is needed to promote thorough evaluation of therapeutic oncology devices, including RODs, in a resource-limited environment, allowing more practical and rapid identification of the most valuable advances in our field.

Error Types and Associations of Clinically Significant Events Within Food and Drug Administration Recalls of Linear Accelerators and Related Products.

PURPOSE: Medical devices in radiation therapy undergo a complex process of Food and Drug Administration (FDA) approval. Little is known about which processes within the radiation therapy medical device industry are most prone to events involving wrong dose, volume, or targeting in radiation therapy treatment. METHODS AND MATERIALS: We carried out a retrospective analysis of the United States FDA Medical Device Recalls database for recalls of products classified as "Accelerator, Linear, Medical" from 2010 to 2016. Each recall event was classified using a modified Delphi method among 3 experts in safety according to product type, error category, and severity score. Error categories included inconvenience; suboptimal plan or treatment; incorrect dose, volume, or targeting; and nonradiation injury risk. Variables investigated were product type, recall year, FDA-determined cause, and quantity of units recalled. Univariate and multivariate logistic regression were used to identify factors prognostic of incorrect dose, volume, or targeting. RESULTS: We identified a total of 250 recall events between 2010 and 2016, with 165 eligible for analysis. Linear accelerators (LINACs) (28%) and LINAC control software (19%) were the most frequently recalled products. The most common FDA-determined causes for recalls were software design (42%) and device design (26%). On univariate analysis (P < .05), LINAC control software (odds ratio [OR] 5.4) and oncology information system or treatment management system (OR 3.9) versus LINACs and software design (OR 3.4) versus device design were associated with wrong dose, volume, or targeting events. On multivariate analysis, only the association with LINAC control software (OR 3.7) persisted for wrong dose, volume, or targeting events. CONCLUSIONS: Review of these data shows that problems with LINAC control software were associated with incorrect dose delivery at a 4-fold higher rate than errors with LINACs. Manufacturers should focus on improvements in software design to minimize dose- and targeting-related errors to patients.

Japanese Structure Survey of Radiation Oncology in 2011.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2012 to August 2015, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2011. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 250 000, respectively. Additionally, the estimated cancer incidence was 851 537 cases with approximately 24.8% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 836), telecobalt (n = 3), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 24), and 192Ir RALS (n = 125). The LINAC system used dual-energy functions in 619 units, 3D conformal radiotherapy functions in 719 and intensity-modulated radiotherapy (IMRT) functions in 412. There were 756 JRS or JASTRO-certified radiation oncologists, 1018.5 full-time equivalent (FTE) radiation oncologists, 2026.7 FTE radiotherapy technologists, 149.1 FTE medical physicists, 141.5 FTE radiotherapy quality managers and 716.3 FTE nurses. The frequency of IMRT use significantly increased during this time. To conclude, although there was a shortage of personnel in 2011, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

Evaluating the Impact of Secure Mobile Messaging on Communication and Cancer Care Team Satisfaction in a Large Radiation Oncology Clinic.

PURPOSE: Communication is crucial in any clinical environment for efficient delivery of care and ensuring patient safety. A 2016 National Database of Nursing Quality Indicators questionnaire indicated poor physician-nurse satisfaction with communication in our department. We addressed gaps in our communication procedures by implementing a communication policy with a secure mobile messaging platform, and we surveyed care team members to evaluate the effectiveness of the implementation. METHODS: We designed a policy around best communication practices and implemented a secure mobile messaging platform, Cureatr, which enables closed-loop, two-way communication that is compliant with the Health Insurance Portability and Accountability Act. Pre- and postimplementation surveys evaluated self-reported impression of efficiency, timeliness, effectiveness, and overall quality of communication, which were scored on a 5-point Likert scale. The number of messages sent was evaluated as a measure of uptake in use, and patient navigation data were queried to measure changes in clinic workflow. RESULTS: After implementation of Cureatr and a communication policy, survey responses demonstrated a clear improvement in staff satisfaction with the efficiency, timeliness, effectiveness, and overall quality of communication. The number of messages sent reflected a progressive increase in use of Cureatr; however, a consistent improvement in clinical workflow as measured by a decrease in patient in-room time was not appreciated. CONCLUSION: Implementing a secure messaging application with a communication policy improved cancer care team satisfaction with communication on all levels. Additional work is needed to evaluate the impact of secure messaging on clinical workflows, patient satisfaction, and staff well-being.

Taking Stock: The Canadian Association of Radiation Oncology 2017 Radiation Oncologist Workforce Study.

PURPOSE: To identify and report radiation oncologist (RO) workforce demographics, clinical workload trends, and equipment inventory in Canada. METHODS AND MATERIALS: The Canadian Association of Radiation Oncology (CARO) distributed an online survey to RO administrative leaders at 47 Canadian cancer centers providing radiation therapy services from June to December 2017. The survey queried RO staff demographics, clinical workload, and equipment inventory from 2014 to 2016. RESULTS: The response rate was 98% and represented 46 of 47 centers for analysis. In 2016, 510 ROs were in practice, with 98 ROs (19.2%) having <1.0 full-time equivalent (FTE) clinical work activities because of administration, research, or part-time employment. Most ROs worked full-time (92.0%), were affiliated with a university (77.5%), and worked in communities with a population >200,000 (84.9%). Approximately half (52.3%) were ≥46 years old. The male-to female ratio was 1.5:1 or higher in all regions of Canada except for Quebec, where there was no gender gap. Part-time employment was more common among female ROs (P < .01). Although FTE staff levels rose steadily between 2014 (456.3) and 2016 (475.8), an increase in patient workload resulted in a rise in the average annual consults per FTE-RO (from 257 to 267). Over a 2-year period, there were 63.5 FTE-recruitments and 44.0 FTE-departures (18.3 FTE-retirements; 25.7 FTE-migration) for a net gain of 19.5 RO-FTEs. An 8.4% increase in FTE staffing to 516 RO-FTEs in 2019 is anticipated, with 22 ROs expected to retire by 2019. There were 251 megavoltage linear accelerators across Canada, with most (39.8%) located in Ontario. Approximately one-fifth (20.7%) of these were older than 10 years and operating beyond the equipment's recommended life span. CONCLUSIONS: The Canadian RO workforce demonstrated incremental growth, but rising annual caseloads suggest that radiation therapy demand outpaced RO supply gains. Government funding is required to replace aging equipment in Canada.

A Current Review of Spatial Fractionation: Back to the Future?

Spatially fractionated radiation therapy represents a significant departure from canonical thinking in radiation oncology despite having origins in the early 1900s. The original and most common implementation of spatially fractionated radiation therapy uses commercially available blocks or multileaf collimators to deliver a nonconfluent, sieve-like pattern of radiation to the target volume in a nonuniform dose distribution. Dosimetrically, this is parameterized by the ratio of the valley dose in cold spots to the peak dose in hot spots, or the valley-to-peak dose ratio. The radiobiologic mechanisms are postulated to involve radiation-induced bystander effects, microvascular alterations, and/or immunomodulation. Current indications include bulky or locally advanced disease that would not be amenable to conventional radiation or that has proved refractory to chemoradiation. Early-phase clinical trials have shown remarkable success, with some response rates >90% and minimal toxicity. This has promoted technological developments in 3-dimensional formats (LATTICE), micron-size beams (microbeam), and proton arrays. Nevertheless, more clinical and biological data are needed to specify ideal dosimetry parameters and to formulate robust clinical indications and guidelines for optimal standardized care.