Automated detection, delineation and quantification of whole-body bone metastasis using FDG-PET/CT images.

Non-small cell lung cancer (NSCLC) patients with the metastatic spread of disease to the bone have high morbidity and mortality. Stereotactic ablative body radiotherapy increases the progression free survival and overall survival of these patients with oligometastases. FDG-PET/CT, a functional imaging technique combining positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) and computer tomography (CT) provides improved staging and identification of treatment response. It is also associated with reduction in size of the radiotherapy tumour volume delineation compared with CT based contouring in radiotherapy, thus allowing for dose escalation to the target volume with lower doses to the surrounding organs at risk. FDG-PET/CT is increasingly being used for the clinical management of NSCLC patients undergoing radiotherapy and has shown high sensitivity and specificity for the detection of bone metastases in these patients. Here, we present a software tool for detection, delineation and quantification of bone metastases using FDG-PET/CT images. The tool extracts standardised uptake values (SUV) from FDG-PET images for auto-segmentation of bone lesions and calculates volume of each lesion and associated mean and maximum SUV. The tool also allows automatic statistical validation of the auto-segmented bone lesions against the manual contours of a radiation oncologist. A retrospective review of FDG-PET/CT scans of more than 30 candidate NSCLC patients was performed and nine patients with one or more metastatic bone lesions were selected for the present study. The SUV threshold prediction model was designed by splitting the cohort of patients into a subset of 'development' and 'validation' cohorts. The development cohort yielded an optimum SUV threshold of 3.0 for automatic detection of bone metastases using FDG-PET/CT images. The validity of the derived optimum SUV threshold on the validation cohort demonstrated that auto-segmented and manually contoured bone lesions showed strong concordance for volume of bone lesion (r = 0.993) and number of detected lesions (r = 0.996). The tool has various applications in radiotherapy, including but not limited to studies determining optimum SUV threshold for accurate and standardised delineation of bone lesions and in scientific studies utilising large patient populations for instance for investigation of the number of metastatic lesions that can be treated safety with an ablative dose of radiotherapy without exceeding the normal tissue toxicity.

Dynamic Contrast-enhanced Magnetic Resonance Imaging Evaluation of Whole Tumour Perfusion Heterogeneity Predicts Distant Disease-free Survival in Locally Advanced Rectal Cancer.

AIMS: To evaluate diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the prediction of disease-free survival (DFS) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy (CRT) and surgery were eligible. Patients underwent multi-parametric magnetic resonance imaging (diffusion-weighted imaging and dynamic contrast-enhanced) before CRT, during CRT (week 3) and after CRT (1 week prior to surgery). Whole tumour apparent diffusion coefficient (ADC) and Ktrans histogram quantiles (10th, 25th, 50th, 75th, 90th) were extracted for analysis. The associations between ADC and Ktrans at three timepoints with time to relapse were analysed as a continuous variable using a Cox proportional hazard model. RESULTS: Thirty-three patients were included in this analysis. The median follow-up was 4.4 years. No patient had locoregional relapse. Nine patients developed distant metastases. The hazard ratios for after CRT Ktrans 10th (P = 0.035), 25th (P = 0.048), 50th (P = 0.046) and 75th (P = 0.045) quantiles were statistically significant for DFS. The best Ktrans cut-off point after CRT for predicting relapse was 28 × 10-3 mL/g/min (10th quantile), with a higher Ktrans value predicting distant relapse. The 4-year DFS probability was 0.93 for patients with after CRT Ktrans value ≤28 × 10-3 mL/g/min versus 0.45 for patients with after CRT Ktrans value >28 × 10-3 mL/g/min. ADC was not able to predict DFS. CONCLUSIONS: Patients with higher Ktrans values after CRT (before surgery) in a histogram analysis of whole tumour heterogeneity had a significantly lower 4-year distant DFS and could be considered for more intense systemic therapy.

Actual Versus Optimal Radiotherapy Utilisation for Metastatic Cancer Patients in the 45 and Up Study Cohort, New South Wales.

AIMS: Radiotherapy can provide quality of life and/or survival benefits to patients with metastatic cancer on diagnosis (MCOD). However, little is known about radiotherapy utilisation in this population. We compared the optimal radiotherapy rates with actual uptake for people who present with MCOD in the 45 and Up Study cohort, and examined factors associated with utilisation. MATERIALS AND METHODS: In total, 267 153 individuals aged ≥45 enrolled in the Sax Institute's 45 and Up Study completed a baseline questionnaire during 2006-2009, providing sociodemographic and health information and consent for linkage to administrative health databases. Participants diagnosed up to December 2013 with MCOD were identified in the New South Wales Cancer Registry. Radiotherapy receipt was determined from claims to the Medicare Benefits Schedule and/or records in the New South Wales Admitted Patient Data Collection (2006 to June 2016). The Collaboration for Cancer Outcomes, Research and Evaluation optimal utilisation model was adapted for patients with MCOD to provide a benchmark. RESULTS: Of 17 687 participants diagnosed with cancer after completion of the baseline questionnaire, 2392 had MCOD. Of patients with MCOD, 25% had primary lung cancer, which was the most common site. The actual radiotherapy utilisation rate for all patients was 32.3%, lower than the optimal of 45.0%. From multivariable analysis, patients who were aged ≥80 years and/or needed help with daily tasks and/or had a Charlson Comorbidity Index ≥2 were less likely to receive radiotherapy. CONCLUSIONS: Actual uptake of radiotherapy was below optimal. Elderly patients and/or those with more comorbidities were less likely to receive radiotherapy. These results suggest a potential role for advocacy and education around radiotherapy for these patient groups.

Patterns of palliative radiotherapy fractionation for brain metastases patients in New South Wales, Australia.

BACKGROUND AND PURPOSE: There is a paucity of studies examining variation in the use of palliative radiation therapy (RT) fractionation for brain metastases. The aim of this study is to assess variation in palliative RT fractionation given for brain metastases in New South Wales (NSW), Australia, and identify factors associated with variation. MATERIALS AND METHODS: This is a population-based cohort of patients who received whole brain RT (WBRT) for brain metastases (2009-2014), as captured in the NSW Central Cancer Registry. A logistic regression model was used to identify factors associated with fractionation type. RESULTS: Of the 2,698 patients that received WBRT, 1,389 courses (51%) were < 6 fractions, 1,050 courses (39%) were 6-10 fractions, and 259 courses (10%) were > 10 fractions. Older patients were more likely to be treated with shorter courses (P < 0.0001). Patients with primary lung cancers were more likely to receive shorter courses compared with other primary cancers (P < 0.0001). Patients without surgical excision were more likely to receive < 6 fractions compared to those who underwent surgical excision. Shorter courses were more likely to be delivered to patients with the most disadvantaged socioeconomic status (SES) compared with patients with the least disadvantaged SES (P < 0.0001). There were significant fluctuations in the proportion of courses using lower number of fractions over time from 2009 to 2014, but no apparent trend (P = 0.02). There was wide variation in the proportion of shorter courses across residence local health districts, ranging from 24% to 69% for < 6 fractions, 21% to 72% for 6-10 fractions, and 4% to 20% for > 10 fractions (P < 0.0001). CONCLUSION: This study has identified significant unwarranted variations in fractionation for WBRT in NSW. Accelerating the uptake of shorter fractionation regimens, if warranted through evidence, should be prioritised to enhance evidence-based care.

Patterns of use of palliative radiotherapy fractionation for bone metastases and 30-day mortality.

BACKGROUND AND PURPOSE: Adoption of single-fraction radiation therapy (SFRT) has not been universal in the palliative treatment of bone metastases, despite evidence supporting its safety and efficacy. The aim of this study was to assess SFRT use for bone metastases in New South Wales (NSW), Australia, and the rate of 30-day mortality (30DM). MATERIALS AND METHODS: This is a population-based cohort of patients who received palliative radiation therapy (RT) for bone metastases (2009-2014), as captured in the NSW Central Cancer Registry. A logistic regression model was used to identify factors associated with fractionation type. The proportion of patients dying within 30-days from treatment start date was calculated. RESULTS: Of the 14,602 courses of palliative RT delivered for bone metastases, 30% were SFRT. SFRT was more likely to be delivered to older patients: ≥80 years (34%) versus < 60 years (28%). Patients with lower socioeconomic status (SES) (35%) were more likely to receive SFRT compared with higher SES (25%). SFRT delivered to patients from outer regional area of residence (34%) were higher compared to those from the major city (29%). The proportion of SFRT delivered to patients with comorbidities ≥2 (34%) was higher than patients with no comorbidity (29%). SFRT was associated with higher 30DM of 21% compared with 11% for multi-fraction RT (MFRT). CONCLUSION: SFRT is underused for the treatment of bone metastases in NSW. This is an impetus to develop tools making SFRT obligatory in this setting unless there is good justification not to.

Anterior skull base olfactory tumours, which is what? A case report and review.

Intracranial schwannomas not originating from cranial nerves are rare. In this paper, we report a case of a 50-year-old male who presented with worsening headaches, diplopia and nausea over two years. Radiological imaging revealed a large tumour arising from the olfactory groove region with a preoperative diagnosis of olfactory groove meningioma (OGM). Intraoperatively, the tumour originated from the region of the attachment of the falx to the crista galli. The patient recovered without complication and histopathology reported an unexpected diagnosis of WHO Grade 1 schwannoma. However, as olfactory groove schwannomas (OGSs) cannot be distinguished from olfactory ensheathing cell tumours (OECTs), it is possible that the tumour could have been either an OGS or an OECT. Distinguishing between OGSs, OECTs and OGMs preoperatively is difficult. OGMs exhibit distinct histopathological features from OGSs/OECTs, however, OGSs and OECTs currently cannot be distinguished from each other. Here, we review the literature to discuss the differentiating features and cellular origins of these three tumours.

Health Economic and Health Service Issues of Palliative Radiotherapy.

Palliative radiotherapy (PRT) makes up about half of all courses delivered in radiotherapy departments. It is effective in the management of common complications of cancer and is relatively inexpensive. About one third of cancer patients receive PRT within the last 2 years of life. One quarter of all patients who receive radiotherapy will undergo a second or subsequent course, mostly for palliative indications. There is considerable variation in practice, both within and between jurisdictions. This has been attributed to inconsistencies in guidelines, physician variation and differing financial incentives. Because of the widespread use of hypofractionation, variation in PRT fractionation has a lower effect on departmental capacity than variation in radical and adjuvant treatments. Excessive fractionation places an unnecessary burden on frail patients at the end of their lives and uses scarce healthcare resources. With appropriate case selection, the increased cost of fractionation or more conformal treatments can be justified where clinical benefit is expected.

Factors Associated With Radiotherapy Utilisation In New South Wales, Australia: Results From The 45 and Up Study.

AIMS: Actual radiotherapy utilisation rates tend to be lower than the estimated optimal rates. Little is known about the factors contributing to this difference. Our aim was to identify factors associated with radiotherapy receipt for a cohort of cancer patients in New South Wales (NSW), Australia. MATERIALS AND METHODS: In total, 267 153 participants in the NSW 45 and Up Study completed a questionnaire during 2006-2009 providing detailed health and socio-demographic information and consented to record linkage with administrative health datasets. Single primary cancers diagnosed after study enrolment were identified through linkage with the NSW Cancer Registry to December 2013. Radiotherapy receipt was determined from claims to the Medicare Benefits Schedule and/or records in the NSW Admitted Patient Data Collection (2006 to June 2016). Competing risks regression was used to examine associations between health and socio-demographic characteristics and radiotherapy treatment. RESULTS: Of 17 873 patients with an incident cancer, 5414 (30.3%) received radiotherapy during follow-up (median 5.3 years). Patients less likely to receive radiotherapy were aged <60 or 80+ years, female, had a Charlson co-morbidity index of 1+, needed help with daily tasks or lived ≥100 km from the nearest radiotherapy centre. CONCLUSION: Distinct subgroups of patients are less likely to receive radiotherapy. Advocacy and/or policy changes are needed to improve access.

Automated electronic discharge summary for patients undergoing acute scrotal exploration: does it improve accuracy and quality?

BACKGROUND: The acute scrotum is a common emergency presentation, and the priority is to exclude testicular torsion, which typically requires scrotal exploration. The accuracy of electronic discharge summaries (EDSs) for patients undergoing acute scrotal exploration has previously been shown to be poor. OBJECTIVE: The objective of this study was to assess accuracy of EDS in patients undergoing acute scrotal exploration in a tertiary paediatric hospital. This study aimed to determine if a new EDS system, whereby the operative procedure is automatically transcribed into the EDS, improves the information within the EDS. METHODS: Retrospective review of the EDS for all patients undergoing acute scrotal exploration between 1st April 2014 and 31st March 2016 was carried out. During this period, a new EDS system, whereby the operative procedure is automatically transcribed to the EDS, was introduced on 20th June 2015. The old system (1st April 2014 to 19th June 2015) was compared with the new system (20th August 2015 to 31st March 2016). RESULTS: A total of 181 patients were included. A diagnosis was not documented in 25 (14%) and was inconsistent with the operation notes in 56 (31%). An operative procedure was not documented at all in 13 (7%) and was inconsistent with the operation notes in 43 (24%). The laterality of pain was not documented and/or incorrect in 11 (6%). The new system in which the operative procedure is automatically transcribed to the EDS resulted in an improvement of diagnoses (78% vs 96%; p = 0.0022; old vs new) and procedures (95% vs 100%; p = 0.0218; old vs new) being documented but not the accuracy. CONCLUSION: The EDS prepared for patients undergoing acute scrotal exploration frequently exhibit inaccuracies; a system that automatically transcribes the operative procedure into the EDS results in modest improvement.

MRI-Linear Accelerator Radiotherapy Systems.

The desire to utilise soft-tissue image guidance at the time of radiation treatment has led to the development of several hybrid magnetic resonance imaging (MRI) linear accelerators (linacs). These systems have the potential to realise the benefits of MRI on the treatment table with the ability of real-time motion management and adaption on a patient-specific basis. There are several MRI-linacs currently being implemented covering both low and high magnetic field strength and two beam-field orientations. Clinical trials have only recently begun with this technology, but their future use as standard radiotherapy practice seems assured. This review article summarises the challenges faced in developing such hybrid technology, the differences and advantages of each of the currently exploited solutions, and their current status.

Imaging performance of a dedicated radiation transparent RF coil on a 1.0 Tesla inline MRI-linac.

This work describes the first imaging studies on a 1.0 Tesla inline MRI-Linac using a dedicated transmit/receive RF body coil that has been designed to be completely radio transparent and provide optimum imaging performance over a large patient opening. A series of experiments was performed on the MRI-Linac to investigate the performance and imaging characteristics of a new dedicated volumetric RF coil: (1) numerical electromagnetic simulations were used to measure transmit efficiency in two patient positions; (2) image quality metrics of signal-to-noise ratio (SNR), ghosting and uniformity were assessed in a large diameter phantom with no radiation beam; (3) radiation induced effects were investigated in both the raw data (k-space) and image sequences acquired with simultaneous irradiation; (4) radiation dose was measured with and without image acquisition; (5) RF heating was studied using an MR-compatible fluoroptic thermometer and; (6) the in vivo image quality and versatility of the coil was demonstrated in normal healthy subjects for both supine and standing positions. Daily phantom measurements demonstrated excellent imaging performance with stable SNR over a period of 3 months (42.6 ± 0.9). Simultaneous irradiation produced no statistical change in image quality (p > 0.74) and no interference in raw data for a 20 × 20 cm radiation field. The coil was found to be efficient over large volumes and negligible RF heating was observed. Volunteer scans acquired in both supine and standing positions provided artefact free images with good anatomical visualisation. The first completely radio transparent RF coil for use on a 1.0 Tesla MRI-Linac has been described. There is no impact on either the imaging or dosimetry performance with a simultaneous radiation beam. The open design enables imaging and radiotherapy guidance in a variety of positons.

Sidney George Shaw, DPhil (1948-2017).

On March 4, 2017 at the age of 68, Sidney George Shaw (Sid) unexpectedly died from complications following surgery, only four years after retiring from the University of Bern. Trained in biochemistry at Oxford University, Sid had quickly moved into molecular pharmacology and became a key investigator in the field of enzyme biochemistry, vasoactive peptide research, and receptor signaling. Sid spent half his life in Switzerland, after moving to the University of Bern in 1984. This article, written by his friends and colleagues who knew him and worked with him during different stages of his career, summarizes his life, his passions, and his achievements in biomedical research. It also includes personal memories relating to a dear friend and outstanding scientist whose intellectual curiosity, humility, and honesty will remain an example to us all.

The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits.

BACKGROUND: To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. METHODS: Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. FINDINGS: 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. INTERPRETATION: Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits.

TRIM28 interacts with EZH2 and SWI/SNF to activate genes that promote mammosphere formation.

Histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) is generally associated with H3K27 methylation and gene silencing, as a member of the polycomb repressor 2 (PRC2) complex. Immunoprecipitation and mass spectrometry of the EZH2-protein interactome in estrogen receptor positive, breast cancer-derived MCF7 cells revealed EZH2 interactions with subunits of chromatin remodeler SWI/SNF complex and TRIM28, which formed a complex with EZH2 distinct from PRC2. Unexpectedly, transcriptome profiling showed that EZH2 primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients. TRIM28 depletion repressed EZH2 recruitment to chromatin and expression of this gene set, in parallel with decreased CD44hi/CD24lo mammosphere formation. Mammosphere formation, inhibited by EZH2 depletion, was rescued by ectopic expression of EZH2 but not by TRIM28 expression or by EZH2 mutated at the region (pre-SET domain) of TRIM28 interaction. These results support PRC2-independent functions of EZH2 and TRIM28 in activation of gene expression that promotes mammary stem cell enrichment and maintenance.

The Benefits of Providing External Beam Radiotherapy in Low- and Middle-income Countries.

More than half of all cancer diagnoses worldwide occur in low- and middle-income countries (LMICs) and the incidence is projected to rise substantially within the next 20 years. Radiotherapy is a vital, cost-effective treatment for cancer; yet there is currently a huge deficit in radiotherapy services within these countries. The aim of this study was to estimate the potential outcome benefits if external beam radiotherapy was provided to all patients requiring such treatment in LMICs, according to the current evidence-based guidelines. Projected estimates of these benefits were calculated to 2035, obtained by applying the previously published Collaboration for Cancer Outcomes, Research and Evaluation (CCORE) demand and outcome benefit estimates to cancer incidence and projection data from the GLOBOCAN 2012 data. The estimated optimal radiotherapy utilisation rate for all LMICs was 50%. There were about 4.0 million cancer patients in LMICs who required radiotherapy in 2012. This number is projected to increase by 78% by 2035, a far steeper increase than the 38% increase expected in high-income countries. National radiotherapy benefits varied widely, and were influenced by case mix. The 5 year population local control and survival benefits for all LMICs, if radiotherapy was delivered according to guidelines, were estimated to be 9.6% and 4.4%, respectively, compared with no radiotherapy use. This equates to about 1.3 million patients who would derive a local control benefit in 2035, whereas over 615 000 patients would derive a survival benefit if the demand for radiotherapy in LMICs was met. The potential outcome benefits were found to be higher in LMICs. These results further highlight the urgent need to reduce the gap between the supply of, and demand for, radiotherapy in LMICs. We must attempt to address this 'silent crisis' as a matter of priority and the approach must consider the complex societal challenges unique to LMICs.

Technical Note: Experimental results from a prototype high-field inline MRI-linac.

PURPOSE: The pursuit of real-time image guided radiotherapy using optimal tissue contrast has seen the development of several hybrid magnetic resonance imaging (MRI)-treatment systems, high field and low field, and inline and perpendicular configurations. As part of a new MRI-linac program, an MRI scanner was integrated with a linear accelerator to enable investigations of a coupled inline MRI-linac system. This work describes results from a prototype experimental system to demonstrate the feasibility of a high field inline MR-linac. METHODS: The magnet is a 1.5 T MRI system (Sonata, Siemens Healthcare) was located in a purpose built radiofrequency (RF) cage enabling shielding from and close proximity to a linear accelerator with inline (and future perpendicular) orientation. A portable linear accelerator (Linatron, Varian) was installed together with a multileaf collimator (Millennium, Varian) to provide dynamic field collimation and the whole assembly built onto a stainless-steel rail system. A series of MRI-linac experiments was performed to investigate (1) image quality with beam on measured using a macropodine (kangaroo) ex vivo phantom; (2) the noise as a function of beam state measured using a 6-channel surface coil array; and (3) electron contamination effects measured using Gafchromic film and an electronic portal imaging device (EPID). RESULTS: (1) Image quality was unaffected by the radiation beam with the macropodine phantom image with the beam on being almost identical to the image with the beam off. (2) Noise measured with a surface RF coil produced a 25% elevation of background intensity when the radiation beam was on. (3) Film and EPID measurements demonstrated electron focusing occurring along the centerline of the magnet axis. CONCLUSIONS: A proof-of-concept high-field MRI-linac has been built and experimentally characterized. This system has allowed us to establish the efficacy of a high field inline MRI-linac and study a number of the technical challenges and solutions.

Estrogens and Coronary Artery Disease: New Clinical Perspectives.

In premenopausal women, endogenous estrogens are associated with reduced prevalence of arterial hypertension, coronary artery disease, myocardial infarction, and stroke. Clinical trials conducted in the 1990s such as HERS, WHI, and WISDOM have shown that postmenopausal treatment with horse hormone mixtures (so-called conjugated equine estrogens) and synthetic progestins adversely affects female cardiovascular health. Our understanding of rapid (nongenomic) and chronic (genomic) estrogen signaling has since advanced considerably, including identification of a new G protein-coupled estrogen receptor (GPER), which like the "classical" receptors ERα and ERß is highly abundant in the cardiovascular system. Here, we discuss the role of estrogen receptors in the pathogenesis of coronary artery disease and review natural and synthetic ligands of estrogen receptors as well as their effects in physiology, on cardiovascular risk factors, and atherosclerotic vascular disease. Data from preclinical and clinical studies using nonselective compounds activating GPER, which include selective estrogen receptor modulators such as tamoxifen or raloxifene, selective estrogen receptor downregulators such as Faslodex™ (fulvestrant/ICI 182,780), vitamin B3 (niacin), green tea catechins, and soy flavonoids such as genistein or resveratrol, strongly suggest that activation of GPER may afford therapeutic benefit for primary and secondary prevention in patients with or at risk for coronary artery disease. Evidence from preclinical studies suggest similar efficacy profiles for selective small molecule GPER agonists such as G-1 which are devoid of uterotrophic activity. Further clinical research in this area is warranted to provide opportunities for future cardiovascular drug development.

A Population-based Model of Local Control and Survival Benefit of Radiotherapy for Lung Cancer.

AIMS: To estimate the population-based locoregional control and overall survival benefits of radiotherapy for lung cancer if the whole population were treated according to evidence-based guidelines. These estimates were based on a published radiotherapy utilisation (RTU) model that has been used to estimate the demand and planning of radiotherapy services nationally and internationally. MATERIALS AND METHODS: The lung cancer RTU model was extended to incorporate an estimate of benefits of radiotherapy alone, and of radiotherapy in conjunction with concurrent chemotherapy (CRT). Benefits were defined as the proportional gains in locoregional control and overall survival from radiotherapy over no radiotherapy for radical indications, and from postoperative radiotherapy over surgery alone for adjuvant indications. A literature review (1990-2015) was conducted to identify benefit estimates of individual radiotherapy indications and summed to estimate the population-based gains for these outcomes. Model robustness was tested through univariate and multivariate sensitivity analyses. RESULTS: If evidence-based radiotherapy recommendations are followed for the whole lung cancer population, the model estimated that radiotherapy alone would result in a gain of 8.3% (95% confidence interval 7.4-9.2%) in 5 year locoregional control, 11.4% (10.8-12.0%) in 2 year overall survival and 4.0% (3.6-4.4%) in 5 year overall survival. For the use of CRT over radiotherapy alone, estimated benefits would be: locoregional control 1.7% (0.8-2.4%), 2 year overall survival 1.7% (0.5-2.8%) and 5 year overall survival 1.2% (0.7-1.9%). CONCLUSIONS: The model provided estimates of radiotherapy benefit that could be achieved if treatment guidelines are followed for all cancer patients. These can be used as a benchmark so that the effects of a shortfall in the utilisation of radiotherapy can be better understood and addressed. The model can be adapted to other populations with known epidemiological parameters to ensure the planning of equitable radiotherapy services.

Cardiovascular effects of pimobendan in healthy mature horses.

REASONS FOR PERFORMING STUDY: Pimobendan is an inodilator used in dogs for the management of heart failure due to myxomatous valve disease or dilated cardiomyopathy. The lack of data regarding the effects of pimobendan in horses prevents the rational use of this drug. OBJECTIVE: To determine the cardiovascular effects of pimobendan in healthy mature horses. STUDY DESIGN: Randomised experimental study. METHODS: Five horses were fasted overnight prior to receiving i.v. pimobendan (0.25 mg/kg bwt), intragastric (i.g.) pimobendan (0.25 mg/kg bwt) or i.g. placebo with a washout period of one week between each administration. Horses were instrumented for the measurement of right ventricular (RV) minimum pressure, RV maximum pressure, RV end diastolic pressure, and maximum rate of increase and decrease in RV pressure before and 0.5, 1, 2, 4, and 8 h after drug administration. Arterial blood pressure, central venous pressure, cardiac output and heart rate were measured at the same time points. Data were expressed as a maximum percentage of change over baseline values. RESULTS: There were no adverse effects associated with administration of pimobendan. The percentage increase in heart rate was significantly greater for horses given pimobendan i.g. (33 ± 4%) and i.v. (36 ± 14%) than for those given a placebo (-2 ± 7%). The percentage increase in maximum rate of increase in RV pressure (35 ± 36%) and the percentage decrease in minimum pressure (47 ± 24%) and end diastolic pressure (34 ± 13%) were significantly greater in horses given pimobendan i.v. than in those given placebo. Other variables measured were not significantly different between treatment groups. CONCLUSION: Pimobendan administered i.v. has positive chronotropic and inotropic effects in healthy mature horses and warrants further investigation for the treatment of heart failure in horses.