Australasian recommendations for quality assurance in kilovoltage radiation therapy from the Kilovoltage Dosimetry Working Group of the Australasian College of Physical Scientists and Engineers in Medicine.

The Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) Radiation Oncology Specialty Group (ROSG) formed a series of working groups to develop recommendations for guidance of radiation oncology medical physics practice within the Australasian setting. These recommendations provide a standard for safe work practices and quality control. It is the responsibility of the medical physicist to ensure that locally available equipment and procedures are sufficiently sensitive to establish compliance. The recommendations are endorsed by the ROSG, have been subject to independent expert reviews and have also been approved by the ACPSEM Council. For the Australian audience, these recommendations should be read in conjunction with the Tripartite Radiation Oncology Practice Standards and should be read in conjunction with relevant national, state or territory legislation which take precedence over the ACPSEM publication Radiation Oncology Reform Implementation Committee (RORIC) Quality Working Group, RANZCR, 2011a; Kron et al. Clin Oncol 27(6):325-329, 2015; Radiation Oncology Reform Implementation Committee (RORIC) Quality Working Group, RANZCR, 2018a, b).

A study on the suitability of the PTW microDiamond detector for kilovoltage x-ray beam dosimetry.

Kilovoltage x-ray beams are widely used in treating skin cancers and in biological irradiators. In this work, we have evaluated four dosimeters (ionization chambers and solid state detectors) in their suitability for relative dosimetry of kilovoltage x-ray beams in the energy range of 50 - 280kVp. The solid state detectors, which have not been investigated with low energy x-rays, were the PTW 60019 microDiamond synthetic diamond detector and the PTW 60012 diode. The two ionization chambers used were the PTW Advanced Markus parallel plate chamber and the PTW PinPoint small volume chamber. For each of the dosimeters, percentage depth doses were measured in water over the full range of x-ray beams and for field sizes ranging from 2cm diameter to 12 × 12cm. In addition, depth doses were measured for a narrow aperture (7mm diameter) using the PTW microDiamond detector. For comparison, the measured data was compared with Monte Carlo calculated doses using the EGSnrc Monte Carlo package. The depth dose results indicate that the Advanced Markus parallel plate and PinPoint ionization chambers were suitable for depth dose measurements in the beam quality range with an uncertainty of less than 3%, including in the regions closer to the surface of the water as compared with Monte Carlo depth dose data for all six energy beams. The response of the PTW Diode E detector was accurate to within 4% for all field sizes in the energy range of 50-125kVp but showed larger variations for higher energies of up to 12% with the 12 × 12cm field size. In comparison, the microDiamond detector had good agreement over all energies for both smaller and larger field sizes generally within 1% as compared to the Advanced Markus chamber field and Monte Carlo calculations. The only exceptions were in measuring the dose at the surface of the water phantom where larger differences were found. For the 7mm diameter field, the agreement between the microDiamond detector and Monte Carlo calculations was good being better than 1% except at the surface. Based on these results, the PTW microDiamond detector has shown to be a suitable detector for relative dosimetry of low energy x-ray beams over a wide range of x-ray beam energies.

Assessment of voluntary deep inspiration breath-hold with CINE imaging for breast radiotherapy.

Deep Inspiration Breath-Hold (DIBH) techniques for breast cancer radiation therapy (RT) have reduced cardiac dose compared to Free Breathing (FB). Recently, a voluntary deep inspiration breath-hold (vDIBH) technique was established using in-room lasers and skin tattoos to monitor breath-hold. An in-house quality assessment of positional reproducibility during RT delivery with vDIBH in patients with left-sided breast cancer was evaluated. The electronic portal imaging device (EPID) was used in cinematographic (CINE) mode to capture a sequence of images during beam delivery. Weekly CINE images were retrospectively assessed for 20 left-sided breast cancer patients receiving RT in vDIBH, and compared with CINE images of 20 patients treated in FB. The intra-beam motion was assessed and the distance from the beam central axis (CA) to the internal chest wall (ICW) was measured on each CINE image. These were then compared to the planned distance on digitally reconstructed radiograph (DRR). The maximum intra-beam motion for any one patient measurement was 0.30 cm for vDIBH and 0.20 cm for FB. The mean difference between the distance from the CA to ICW on DRR and the equivalent distance on CINE imaging (as treated) was 0.28 cm (SD 0.17) for vDIBH patients and 0.25 cm (SD 0.14) for FB patients (P = 0.458). The measured values were comparable for patients undergoing RT in vDIBH, and for those in FB. This quality assessment showed that using in-room lasers and skin tattoos to independently monitor breath-hold in vDIBH as detected by 'on-treatment' CINE imaging is safe and effective.

Practical time considerations for optically stimulated luminescent dosimetry (OSLD) in total body irradiation.

Total body irradiation (TBI) treatments are used to treat the whole body in preparation for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy in 6 fraction, bi-daily technique using 6 MV X-rays at an extended Source-to-Surface distance (SSD) of 300 cm. Utilizing these characteristics, the beam dose rate is reduced below 7 cGy/min as is standard for TBI treatment. Dose received by the patient is monitored using optically stimulated luminescent dosimetry (OSLD). This work presents some practical calibration corrections based on time-dependant factors for OSLD calibration related to TBI procedure. Results have shown that a negligible difference is seen in OSL sensitivity for 6 MV X-rays irradiated in standard SSD (100 cm) and high dose rate (600 cGy/min) conditions compared to extended SSD (300 cm) and low TBI dose rate (6 cGy/min) conditions. Results have also shown that whilst short term signal fading occurs in the OSL after irradiation at a high dose rate (37% reduction in signal in the first 15 min), thereafter, negligible differences are seen in the OSL signal between 600 and 7 cGy/min irradiations. Thus a direct comparison can be made between calibration OSLs and clinical TBI OSLs between 15 min and 2 h. Finally a table is presented to provide corrections between calibration OSL readout and clinical TBI dose readout for a period up to 7 days. Combining these three results allows users to pre-irradiate their calibration OSLs at standard dose rate and SSD, up to 1 week prior to clinical treatment, and still provide accurate in-vivo dosimetry. This can help with time saving and work efficiency in the clinic.

Using LASSO Regression to Predict Rheumatoid Arthritis Treatment Efficacy.

Rheumatoid arthritis (RA) accounts for one-fifth of the deaths due to arthritis, the leading cause of disability in the United States. Finding effective treatments for managing arthritis symptoms are a major challenge, since the mechanisms of autoimmune disorders are not fully understood and disease presentation differs for each patient. The American College of Rheumatology clinical guidelines for treatment consider the severity of the disease when deciding treatment, but do not include any prediction of drug efficacy. Using Electronic Health Records and Biomedical Linked Open Data (LOD), we demonstrate a method to classify patient outcomes using LASSO penalized regression. We show how Linked Data improves prediction and provides insight into how drug treatment regimes have different treatment outcome. Applying classifiers like this to decision support in clinical applications could decrease time to successful disease management, lessening a physical and financial burden on patients individually and the healthcare system as a whole.

In vivo dosimetric impact of breast tissue expanders on post-mastectomy radiotherapy.

INTRODUCTION: Temporary tissue expanders with metallic ports for gradual saline injection are increasingly employed to facilitate breast reconstruction after post-mastectomy radiotherapy (PMRT). Treatment beams therefore pass through a high-density rare-earth magnet. Measurements ex vivo suggest attenuation of dose to the skin and chest wall at clinical risk of relapse. The purpose of the study was to quantify the resulting dose reduction in vivo, compared with treatment planning system (TPS). METHODS: Sixteen patients receiving PMRT had in vivo dosimetry prospectively performed with ethics board approval. Port was located within the expanded chest wall using the planning CT scan. Strips of radiochromic film were laid on the skin surface underneath the bolus. To aid interpretation, ex vivo measurements were also performed, including comparison with TPS predictions. RESULTS: An average 7% reduction in dose to skin surface was measured in 15 of 16 patients. This was reproducibly located in the 'shadow' of the magnet, corresponding to each of the paths of the medial and lateral tangents. The average area was 1.07 cm(2) (range 0.39 cm(2) to 2.36 cm(2)). Ex vivo measurements confirmed attenuation of the beam in the shadow of the port. The surface area of the 'cold-spot' varied with angle of the beam relative to the metallic port. Dose attenuation in vivo differed from that predicted by the TPS. CONCLUSION: Dose is attenuated in the 'shadow' of the tissue expander port in patients receiving PMRT. This is likely to be clinically insignificant for most, but centres should undertake appropriate measurements before utilising TPS predictions.

Mining Electronic Health Records using Linked Data.

Meaningful Use guidelines have pushed the United States Healthcare System to adopt electronic health record systems (EHRs) at an unprecedented rate. Hospitals and medical centers are providing access to clinical data via clinical data warehouses such as i2b2, or Stanford's STRIDE database. In order to realize the potential of using these data for translational research, clinical data warehouses must be interoperable with standardized health terminologies, biomedical ontologies, and growing networks of Linked Open Data such as Bio2RDF. Applying the principles of Linked Data, we transformed a de-identified version of the STRIDE into a semantic clinical data warehouse containing visits, labs, diagnoses, prescriptions, and annotated clinical notes. We demonstrate the utility of this system though basic cohort selection, phenotypic profiling, and identification of disease genes. This work is significant in that it demonstrates the feasibility of using semantic web technologies to directly exploit existing biomedical ontologies and Linked Open Data.

Analyzing search behavior of healthcare professionals for drug safety surveillance.

Post-market drug safety surveillance is hugely important and is a significant challenge despite the existence of adverse event (AE) reporting systems. Here we describe a preliminary analysis of search logs from healthcare professionals as a source for detecting adverse drug events. We annotate search log query terms with biomedical terminologies for drugs and events, and then perform a statistical analysis to identify associations among drugs and events within search sessions. We evaluate our approach using two different types of reference standards consisting of known adverse drug events (ADEs) and negative controls. Our approach achieves a discrimination accuracy of 0.85 in terms of the area under the receiver operator curve (AUC) for the reference set of well-established ADEs and an AUC of 0.68 for the reference set of recently labeled ADEs. We also find that the majority of associations in the reference sets have support in the search log data. Despite these promising results additional research is required to better understand users' search behavior, biasing factors, and the overall utility of analyzing healthcare professional search logs for drug safety surveillance.

Text mining for adverse drug events: the promise, challenges, and state of the art.

Text mining is the computational process of extracting meaningful information from large amounts of unstructured text. It is emerging as a tool to leverage underutilized data sources that can improve pharmacovigilance, including the objective of adverse drug event (ADE) detection and assessment. This article provides an overview of recent advances in pharmacovigilance driven by the application of text mining, and discusses several data sources-such as biomedical literature, clinical narratives, product labeling, social media, and Web search logs-that are amenable to text mining for pharmacovigilance. Given the state of the art, it appears text mining can be applied to extract useful ADE-related information from multiple textual sources. Nonetheless, further research is required to address remaining technical challenges associated with the text mining methodologies, and to conclusively determine the relative contribution of each textual source to improving pharmacovigilance.

A time-indexed reference standard of adverse drug reactions.

Undetected adverse drug reactions (ADRs) pose a major burden on the health system. Data mining methodologies designed to identify signals of novel ADRs are of deep importance for drug safety surveillance. The development and evaluation of these methodologies requires proper reference benchmarks. While progress has recently been made in developing such benchmarks, our understanding of the performance characteristics of the data mining methodologies is limited because existing benchmarks do not support prospective performance evaluations. We address this shortcoming by providing a reference standard to support prospective performance evaluations. The reference standard was systematically curated from drug labeling revisions, such as new warnings, which were issued and communicated by the US Food and Drug Administration in 2013. The reference standard includes 62 positive test cases and 75 negative controls, and covers 44 drugs and 38 events. We provide usage guidance and empirical support for the reference standard by applying it to analyze two data sources commonly mined for drug safety surveillance.

Near-catheter dosimetry of a HDR brachytherapy source using Gafchromic film.

High dose rate intraluminal brachytherapy treatments can be delivered using as few as one or two afterloading catheters, delivering doses of up to 10 Gy at 10 mm, leading to high dose gradients and extreme hot spots close to the catheter. These conditions have the potential to damage the patient's health tissues, possibly leading to necrosis, or even death from uncontrolled bleeding. Ionisation chambers and solid state detectors are limited in their usefulness for near-catheter dosimetry because of their physical size and in some cases energy and dose rate dependence. In contrast, radiochromic film has a large dose-response range, excellent spatial resolution, near-energy independence for megavoltage photons and the ability to measure dose in two dimensions, making it ideal for this application. The aim of this study was to measure the location and relative magnitude of any dosimetric hot spots produced by a typical endobronchial treatment plan. The study also investigated the effect of the step size of the (192)Ir source on both the dose hot spots and dose distribution. Our measurements show that for a typical single catheter treatment with 2.5 mm step size the maximum dose hot spots at the catheter surface are up to 37 times the prescription dose, up to 40 times for a 5 mm step size, and up to 46 times for a 10 mm step size. It is important that brachytherapy clinicians and physicists understand that hot spot magnitude increases with source step sizes and are aware of the risks associated with this form of brachytherapy treatment.

Methyl 3-[3',4'-(methylenedioxy)phenyl]-2-methyl glycidate: an ecstasy precursor seized in Sydney, Australia.

Five 44 gallon drums labeled as glycidyl methacrylate were seized by the Australian Customs Service and the Australian Federal Police at Port Botany, Sydney, Australia, in December 2004. Each drum contained a white, semisolid substance that was initially suspected to be 3,4-methylenedioxymethylamphetamine (MDMA). Gas chromatography-mass spectroscopy (GC/MS) analysis demonstrated that the material was neither glycidyl methacrylate nor MDMA. Because intelligence sources employed by federal agents indicated that this material was in some way connected to MDMA production, suspicion fell on the various MDMA precursor chemicals. Using a number of techniques including proton nuclear magnetic resonance spectroscopy ((1)H NMR), carbon nuclear magnetic resonance spectroscopy ((13)C NMR), GC/MS, infrared spectroscopy, and total synthesis, the unknown substance was eventually identified as methyl 3-[3',4'(methylenedioxy)phenyl]-2-methyl glycidate. The substance was also subjected to a published hydrolysis and decarboxylation procedure and gave a high yield of the MDMA precursor chemical, 3,4-methylenedioxyphenyl-2-propanone, thereby establishing this material as a "precursor to a precursor."