Challenges in the Sustainability of Brachytherapy Service in Contemporary Radiotherapy.

Brachytherapy has a long history of delivering a highly conformal radiation dose to the target volume with sparing of adjacent normal tissue and has an irreplaceable role in certain cancers, such as cervical and prostate cancers. There have been futile attempts to replace brachytherapy with other radiation techniques. Despite that there are multifaceted challenges in preserving this dying art, from establishment, to a trained workforce, to maintenance of the equipment and source replacement costs. Here we focus on the challenges to access brachytherapy, the availability and distribution of care across the globe and appropriate training leading to proper implementation of the procedure. Brachytherapy holds a significant place in the treatment armamentarium of most common cancers, such as cervical, prostate, head and neck and skin cancers. However, there is an uneven distribution of brachytherapy facilities, not only across the globe, but also at a national level, with a larger proportion of facilities concentrated in certain regions, more so in low and low-middle income countries. The regions with the highest incidence of cervical cancer have the least access to brachytherapy facilities. Attempts to bridge the gap are essential and should be focused on uniform distribution and access to care, improving training of the workforce through specialised training programmes, reducing the cost of care, planning to reduce the recurring cost, generating evidence and research guidelines, renewing interest in brachytherapy through rebranding, use of social media and building an attainable long-term roadmap.

Modern Tools for Modern Brachytherapy.

This review aims to showcase the brachytherapy tools and technologies that have emerged during the last 10 years. Soft-tissue contrast using magnetic resonance and ultrasound imaging has seen enormous growth in use to plan all forms of brachytherapy. The era of image-guided brachytherapy has encouraged the development of advanced applicators and given rise to the growth of individualised 3D printing to achieve reproducible and predictable implants. These advances increase the quality of implants to better direct radiation to target volumes while sparing normal tissue. Applicator reconstruction has moved beyond manual digitising, to drag and drop of three-dimensional applicator models with embedded pre-defined source pathways, ready for auto-recognition and automation. The simplified TG-43 dose calculation formalism directly linked to reference air kerma rate of high-energy sources in the medium water remains clinically robust. Model-based dose calculation algorithms accounting for tissue heterogeneity and applicator material will advance the field of brachytherapy dosimetry to become more clinically accurate. Improved dose-optimising toolkits contribute to the real-time and adaptive planning portfolio that harmonises and expedites the entire image-guided brachytherapy process. Traditional planning strategies remain relevant to validate emerging technologies and should continue to be incorporated in practice, particularly for cervical cancer. Overall, technological developments need commissioning and validation to make the best use of the advanced features by understanding their strengths and limitations. Brachytherapy has become high-tech and modern by respecting tradition and remaining accessible to all.

TROG 14.04: Multicentre Study of Feasibility and Impact on Anxiety of DIBH in Breast Cancer Patients.

AIMS: The aim of TROG 14.04 was to assess the feasibility of deep inspiration breath hold (DIBH) and its impact on radiation dose to the heart in patients with left-sided breast cancer undergoing radiotherapy. Secondary end points pertained to patient anxiety and cost of delivering a DIBH programme. MATERIALS AND METHODS: The study comprised two groups - left-sided breast cancer patients engaging DIBH and right-sided breast cancer patients using free breathing through radiotherapy. The primary end point was the feasibility of DIBH, defined as left-sided breast cancer patients' ability to breath hold for 15 s, decrease in heart dose in DIBH compared with the free breathing treatment plan and reproducibility of radiotherapy delivery using mid-lung distance (MLD) assessed on electronic portal imaging as the surrogate. The time required for treatment delivery, patient-reported outcomes and resource requirement were compared between the groups. RESULTS: Between February and November 2018, 32 left-sided and 30 right-sided breast cancer patients from six radiotherapy centres were enrolled. Two left-sided breast cancer patients did not undergo DIBH (one treated in free breathing as per investigator choice, one withdrawn). The mean heart dose was reduced from 2.8 Gy (free breathing) to 1.5 Gy (DIBH). Set-up reproducibility in the first week of treatment assessed by MLD was 1.88 ± 1.04 mm (average ± 1 standard deviation) for DIBH and 1.59 ± 0.93 mm for free breathing patients. Using a reproducibility cut-off for MLD of 2 mm (1 standard deviation) as per study protocol, DIBH was feasible for 67% of DIBH patients. Radiotherapy delivery using DIBH took about 2 min longer than for free breathing. Anxiety was not significantly different in DIBH patients and decreased over the course of treatment in both groups. CONCLUSION: Although DIBH was shown to require about 2 min longer per treatment slot, it has the potential to reduce heart dose in left-sided breast cancer patients by nearly a half, provided careful assessment of breath hold reproducibility is carried out.

An international survey of imaging practices in radiotherapy.

Improvements in delivery of radiation dose to target tissues in radiotherapy have increased the need for better image quality and led to a higher frequency of imaging patients. Imaging for treatment planning extends to function and motion assessment and devices are incorporated into medical linear accelerators (linacs) so that regions of tissue can be imaged at time of treatment delivery to ensure dose distributions are delivered as accurately as possible. A survey of imaging in 97 radiotherapy centres in nine countries on six continents has been undertaken with an on-line questionnaire administered through the International Commission on Radiological Protection mentorship programme to provide a snapshot of imaging practices. Responses show that all centres use CT for planning treatments and many utilise additional information from magnetic resonance imaging and positron emission tomography scans. Most centres have kV cone beam CT attached to at least some linacs and use this for the majority of treatment fractions. The imaging options available declined with the human development index (HDI) of the country, and the frequency of imaging during treatment depended more on country than treatment site with countries having lower HDIs imaging less frequently. The country with the lowest HDI had few kV imaging facilities and relied on MV planar imaging intermittently during treatment. Imaging protocols supplied by vendors are used in most centres and under half adapt exposure conditions to individual patients. Recording of patient doses, a knowledge of which is important in optimisation of imaging protocols, was limited primarily to European countries.

A validation framework to assess performance of commercial deformable image registration in lung radiotherapy.

INTRODUCTION: Deformable image registration (DIR) can play an important role in the context of adaptive radiotherapy. The AAPM Task Group 132 (TG-132) has described several quantitative measures for DIR error assessment but they can only be accurately defined when there is a ground-truth present in high-contrast regions. This work aims to set out a framework to obtain optimal results for CT-CT lung DIR in clinical setting for a commercially available system by quantifying the DIR performance in both low- and high-contrast regions. METHODS: Five publicly available thorax datasets were used to assess the DIR quality. A "Ghost fiducial" method was implemented by windowing the contrast in a new feature provided by Varian Velocity v4.1. Target registration error (TRE) of the landmarks and Dice-similarity coefficient of the tumour were calculated at three different contrast settings to assess the algorithm in high- and low-contrast scenarios. RESULTS: For the original unedited dataset, higher resolution DIR methods showed best performance acceptable within the recommended limit according to TG-132, when actual displacements were less than 10 mm. The relation of the actual displacement of the landmarks and TRE shows the limited capacity of the algorithm to deal with movements larger than 10 mm. CONCLUSION: This work found the performance of DIR methods and settings available in Varian Velocity v4.1 to be a function of contrast level as well as extent of motion. This highlights the need for multiple metrics to assess different aspects of DIR performance for various applications related to low-contrast and/or high-contrast regions.

Assessment of Intrafraction Motion of the Urinary Bladder Using Magnetic Resonance Imaging (cineMRI).

AIM: To assess the intrafraction motion of the urinary bladder and delineate the appropriate margin size for radiotherapy planning, for both the full and empty bladder. MATERIALS AND METHODS: This was a single-site, single-arm study of 20 patients planned to undergo radical cystectomy for histologically confirmed muscle-invasive bladder cancer. Patients underwent magnetic resonance imaging (cineMRI) of the entire pelvis using a 3-Tesla system, prior to cystectomy. Patients first underwent a cineMRI with a full bladder, then voided and underwent a second MRI with an empty bladder. All MRI sequences were acquired over 18 min. We assessed the differences in bladder filling and subsequent bladder wall displacement, between the empty and full bladder, during a time period consistent with radiotherapy treatment delivery. RESULTS: Twenty patients underwent cineMRI of the entire pelvis. The maximum mean directional displacements of the bladder walls over the 18 min duration of the scan for the empty bladders were 9.8 mm superiorly, 1.1 mm inferiorly, 2.39 mm anteriorly, 3.73 mm posteriorly, 2.74 mm to the left and 2.48 mm to the right. The maximal mean displacements for the full bladders were 9.2 mm superiorly, 1.1 mm inferiorly, 2.28 mm anteriorly, 1.08 mm posteriorly, 1.85 mm to the left and 1.73 mm to the right. Statistically significant differences were seen in the posterior, left and right displacements but were quantitatively small. CONCLUSIONS: Intrafractional motion secondary to bladder filling showed minimal variation between the full and empty bladder. Similar clinical target volume to planning target volume margins can be applied for the delivery of radiotherapy for a full and empty bladder.

Gyroid structures for 3D-printed heterogeneous radiotherapy phantoms.

The extreme customisation and rapid prototyping capabilities of the 3D printing process allows the manufacture of low-cost and patient-specific radiotherapy phantoms for quality assurance purposes. However, the associated printing techniques and materials are experimentally limited and are yet to be quantified in terms of manufacturability. In addition to this, there lacks research in utilising naturally inspired structures, known as triply periodic minimal surfaces (TPMS), as a structural manufacturing basis for these phantoms, enabling material heterogeneity, which is a significant factor in attaining patient-specificity. We propose the use of Gyroid structures for radiotherapy phantom applications to investigate Gyroid-phantom manufacturability, the mathematical definition of Gyroids and their effects on hounsfield units (HU). The printed Gyroid phantoms were assessed for manufacturability using optical microscopy and micro-computed tomography (µCT), and material hounsfield-equivalence using standard medical CT. A mean HU range of -900 to -390 were achieved from the fabricated Gyroid phantoms with varying standard deviation. Compared to traditional printing infills such as grid and slit structures, the Gyroid phantoms were observed to produce isotropic HU and SD at varied scanning orientations, which optimizes CT attenuations in modulating the hounsfield-equivalence of printed structures. This study not only demonstrates the feasibility of manipulating the structural parameters of Gyroids in simulating tissue imaging attenuations but also opens significant research opportunities in fabricating patient-specific phantoms with added pathological features for end-to-end radiotherapy testing.

2D monolithic silicon-diode array detectors in megavoltage photon beams: does the fabrication technology matter? A medical physicist's perspective.

A family of prototype 2D monolithic silicon-diode array detectors (MP512, Duo, Octa) has been proposed by the Centre for Medical Radiation Physics, University of Wollongong (Australia) for relative dosimetry in small megavoltage photon beams. These detectors, which differ in the topology of their 512 sensitive volumes, were originally fabricated on bulk p-type substrates. More recently, they have also been fabricated on epitaxial p-type substrates. In the literature, their performance has been individually characterized for quality assurance (QA) applications. The present study directly assessed and compared that of a MP512-bulk and that of a MP512-epitaxial in terms of radiation hardness, long-term stability, response linearity with dose, dose per pulse and angular dependence. Their measurements of output factors, off-axis ratios and percentage depth doses in square radiation fields collimated by the jaws and produced by 6 MV and 10 MV flattened photon beams were then benchmarked against those by commercially available detectors. The present investigation was aimed at establishing, from a medical physicist's perspective, how the bulk and epitaxial fabrication technologies would affect the implementation of the MP512s into a QA protocol. Based on results, the MP512-epitaxial would offer superior radiation hardness, long-term stability and achievable uniformity and reproducibility of the response across the 2D active area.

A novel high-resolution 2D silicon array detector for small field dosimetry with FFF photon beams.

PURPOSE: Flattening filter free (FFF) beams are increasingly being considered for stereotactic radiotherapy (SRT). For the first time, the performance of a monolithic silicon array detector under 6 and 10 MV FFF beams was evaluated. The dosimeter, named "Octa" and designed by the Centre for Medical Radiation Physics (CMRP), was tested also under flattened beams for comparison. METHODS: Output factors (OFs), percentage depth-dose (PDD), dose profiles (DPs) and dose per pulse (DPP) dependence were investigated. Results were benchmarked against commercially available detectors for small field dosimetry. RESULTS: The dosimeter was shown to be a 'correction-free' silicon array detector for OFs and PDD measurements for all the beam qualities investigated. Measured OFs were accurate within 3% and PDD values within 2% compared against the benchmarks. Cross-plane, in-plane and diagonal DPs were measured simultaneously with high spatial resolution (0.3 mm) and real time read-out. A DPP dependence (24% at 0.021 mGy/pulse relative to 0.278 mGy/pulse) was found and could be easily corrected for in the case of machine specific quality assurance applications. CONCLUSIONS: Results were consistent with those for monolithic silicon array detectors designed by the CMRP and previously characterized under flattened beams only, supporting the robustness of this technology for relative dosimetry for a wide range of beam qualities and dose per pulses. In contrast to its predecessors, the design of the Octa offers an exhaustive high-resolution 2D dose map characterization, making it a unique real-time radiation detector for small field dosimetry for field sizes up to 3 cm side.

Single Fraction Stereotactic Ablative Body Radiotherapy for Oligometastasis: Outcomes from 132 Consecutive Patients.

AIMS: Stereotactic ablative body radiotherapy (SABR) is currently used to treat oligometastases, but the optimum dose/fractionation schedule is unknown. In this study, we evaluated outcomes after single fraction SABR in patients with oligometastatic disease. MATERIALS AND METHODS: Single institutional retrospective review of patients treated with single fraction SABR for one to three oligometastases between 2010 and 2015. The primary outcome was freedom from widespread disease defined as distant recurrence not amenable to surgery or SABR; or recurrence with four or more metastases. RESULTS: In total, 186 treatments were delivered in 132 patients. The two most common target sites were lung (51%) and bone (40%). The most frequent single fraction prescription dose was 26 Gy (47%). The most common primary malignancy was genitourinary (n = 46 patients). Freedom from widespread disease was 75% at 1 year (95% confidence interval 67-83%) and 52% at 2 years (95% confidence interval 42-63%). Freedom from local progression at 1 year was 90% (95% confidence interval 85-95%) and at 2 years was 84% (95% confidence interval 77-91%). A compression fracture of the lumbar vertebra was the only grade 3+ treatment-related toxicity. CONCLUSIONS: Single fraction SABR is associated with a high rate of freedom from widespread disease, favourable local control and low toxicity comparable with historic multi-fraction SABR reports.

Out-of-field in vivo dosimetry using TLD in SABR for primary kidney cancer involving mixed photon fields.

PURPOSE: To assess out-of-field dose using three different variants of LiF thermoluminescence dosimeters (TLD) for ten patients who underwent stereotactic ablative body radiotherapy (SABR) for primary renal cell carcinoma (RCC) and compare with treatment planning system (TPS) dose calculations. METHODS AND MATERIALS: Thermoluminescent dosimeter (TLD) measurements were conducted at 20, 30, 40 and 50cm from isocentre on ten patients undergoing SABR for primary RCC. Three types of high-sensitivity LiF:Mg,Cu,P TLD material with different 6Li/7Li isotope ratios were used. Patient plans were calculated using Eclipse Anisotropic Analytical Algorithm (AAA) for clinical evaluation and recalculated using Pencil Beam Convolution (PBC) algorithm for comparison. RESULTS: Both AAA and PBC showed diminished accuracy for photon doses at increasing distance out-of-field. At 50cm, measured photon dose was 0.3cGy normalised to a 10Gy prescription on average with only small variation across all patients. This is likely due to the leakage component of the out-of-field dose. The 6Li-enriched TLD materials showed increased signal attributable to additional neutron contribution. CONCLUSION: LiF:Mg,Cu,P TLD containing 6Li is sensitive enough to measure out-of-field dose 50cm from isocentre however will over-estimate the photon component of out-of-field dose in high energy treatments due to the presence of thermal neutrons. 7Li enriched materials which are insensitive to neutrons are therefore required for accurate photon dosimetry. Neutron signal has been shown here to increase with MUs and is higher for patients treated using certain non coplanar beam arrangements. Further work is required to convert this additional neutron signal to dose.

Towards high-resolution laser ionization spectroscopy of the heaviest elements in supersonic gas jet expansion.

Resonant laser ionization and spectroscopy are widely used techniques at radioactive ion beam facilities to produce pure beams of exotic nuclei and measure the shape, size, spin and electromagnetic multipole moments of these nuclei. However, in such measurements it is difficult to combine a high efficiency with a high spectral resolution. Here we demonstrate the on-line application of atomic laser ionization spectroscopy in a supersonic gas jet, a technique suited for high-precision studies of the ground- and isomeric-state properties of nuclei located at the extremes of stability. The technique is characterized in a measurement on actinium isotopes around the N=126 neutron shell closure. A significant improvement in the spectral resolution by more than one order of magnitude is achieved in these experiments without loss in efficiency.

Real-time Image-guided Adaptive-predictive Prostate Radiotherapy using Rectal Diameter as a Predictor of Motion.

AIMS: To investigate a relationship between maximum rectal diameter (MRD) on pre-treatment cone beam computed tomography (CBCT) and intra-fraction prostate motion, in the context of an adaptive image-guided radiotherapy (IGRT) method. MATERIALS AND METHODS: The MRD was measured on 2125 CBCTs from 55 retrospective patient datasets and related to prostate displacement from intra-fraction imaging. A linear regression model was developed to determine a threshold MRD associated with a high probability of small prostate displacement. Standard and reduced adaptive margin plans were created to compare rectum and bladder normal tissue complication probability (NTCP) with each method. RESULTS: A per-protocol analysis carried out on 1910 fractions from 51 patients showed with 90% confidence that for a MRD≤3 cm, prostate displacement will be ≤5 mm and that for a MRD≤3.5 cm, prostate displacement will be ≤5.5 mm. In the first scenario, if adaptive therapy was used instead of standard therapy, median reductions in NTCP for rectum and bladder were 0.5% (from 9.5% to 9%) and 1.3% (from 6.6% to 5.3%), respectively. In the second scenario, the NTCP for rectum and bladder would have median reductions of 1.1% and 2.6%, respectively. CONCLUSIONS: We have identified a potential method for adaptive prostate IGRT based upon predicting small prostate intra-fraction motion by measuring MRD on pre-treatment CBCT.

A Multidisciplinary Evaluation of a Web-based eLearning Training Programme for SAFRON II (TROG 13.01): a Multicentre Randomised Study of Stereotactic Radiotherapy for Lung Metastases.

AIMS: In technically advanced multicentre clinical trials, participating centres can benefit from a credentialing programme before participating in the trial. Education of staff in participating centres is an important aspect of a successful clinical trial. In the multicentre study of fractionated versus single fraction stereotactic ablative body radiotherapy in lung oligometastases (TROG 13.01), knowledge transfer of stereotactic ablative body radiotherapy techniques to the local multidisciplinary team is intended as part of the credentialing process. In this study, a web-based learning platform was developed to provide education and training for the multidisciplinary trial teams at geographically distinct sites. MATERIALS AND METHODS: A web-based platform using eLearning software consisting of seven training modules was developed. These modules were based on extracranial stereotactic theory covering the following discrete modules: Clinical background; Planning technique and evaluation; Planning optimisation; Four-dimensional computed tomography simulation; Patient-specific quality assurance; Cone beam computed tomography and image guidance; Contouring organs at risk. Radiation oncologists, medical physicists and radiation therapists from hospitals in Australia and New Zealand were invited to participate in this study. Each discipline was enrolled into a subset of modules (core modules) and was evaluated before and after completing each module. The effectiveness of the eLearning training will be evaluated based on (i) knowledge retention after participation in the web-based training and (ii) confidence evaluation after participation in the training. Evaluation consisted of a knowledge test and confidence evaluation using a Likert scale. RESULTS: In total, 130 participants were enrolled into the eLearning programme: 81 radiation therapists (62.3%), 27 medical physicists (20.8%) and 22 radiation oncologists (16.9%). There was an average absolute improvement of 14% in test score (P < 0.001) after learning. This score improvement compared with initial testing was also observed in the long-term testing (>4 weeks) after completing the modules (P < 0.001). For most there was significant increase in confidence (P < 0.001) after completing all the modules.

Optimization of a hot-cavity type resonant ionization laser ion source.

Resonant Ionization Laser Ion Source (RILIS) is nowadays an important technique in many Radioactive Ion Beam (RIB) facilities for its reliability and ability to ionize efficiently and element selectively. Grand Accélérateur National d'Ions Lourds (GANIL) Ion Source using Electron Laser Excitation (GISELE) is an off-line test bench for RILIS developed to study a fully operational resonant laser ion source at GANIL facility. The ion source body has been designed as a modular system to investigate different experimental approaches by varying the design parameters, to develop the future on-line laser ion source. The aim of this project is to determine the best technical solution which combines high selectivity and ionization efficiency with small ion beam emittance and stable long term operation. Latest results concerning emittance and time profile development as a function of the temperature for different ion source versions will be presented.

DOSE AND GAMMA-RAY SPECTRA FROM NEUTRON-INDUCED RADIOACTIVITY IN MEDICAL LINEAR ACCELERATORS FOLLOWING HIGH-ENERGY TOTAL BODY IRRADIATION.

Production of radioisotopes in medical linear accelerators (linacs) is of concern when the beam energy exceeds the threshold for the photonuclear interaction. Staff and patients may receive a radiation dose as a result of the induced radioactivity in the linac. Gamma-ray spectroscopy was used to identify the isotopes produced following the delivery of 18 MV photon beams from a Varian 21EX and an Elekta Synergy. The prominent radioisotopes produced include 187W, 63Zn, 56Mn, 24Na and 28Al in both linac models. The dose rate was measured at the beam exit window (12.6 µSv in the first 10 min) following 18 MV total body irradiation (TBI) beams. For a throughput of 24 TBI patients per year, staff members are estimated to receive an annual dose of up to 750 µSv at the patient location. This can be further reduced to 65 µSv by closing the jaws before re-entering the treatment bunker.

Brief histories of medical physics in Asia-Oceania.

The history of medical physics in Asia-Oceania goes back to the late nineteenth century when X-ray imaging was introduced, although medical physicists were not appointed until much later. Medical physics developed very quickly in some countries, but in others the socio-economic situation as such prevented it being established for many years. In others, the political situation and war has impeded its development. In many countries their medical physics history has not been well recorded and there is a danger that it will be lost to future generations. In this paper, brief histories of the development of medical physics in most countries in Asia-Oceania are presented by a large number of authors to serve as a record. The histories are necessarily brief; otherwise the paper would quickly turn into a book of hundreds of pages. The emphasis in each history as recorded here varies as the focus and culture of the countries as well as the length of their histories varies considerably.