Immediate versus expedient emergent laparotomy in unstable isolated abdominal trauma patients.

INTRODUCTION: Unstable abdominal trauma patients should be treated with emergent laparotomy. However, few studies have evaluated the association between time to surgery and survival in these patients. We aimed to assess the influence of time to laparotomy on outcomes in blunt and penetrating unstable abdominal trauma patients. METHODS: This retrospective study includes patients with abdominal injuries, systolic blood pressure <90mmHg on arrival, admitted in Israel during 2000-2018. Data regarding patients' characteristics, Injury Severity Score (ISS), Glasgow Coma Scale (GCS), time to surgery, length of hospital stay and mortality were collected via The Israeli National Trauma Registry. RESULTS: Overall, 69 blunt and 127 penetrating injury patients were included in the study. For blunt and penetrating trauma patients with ISS ≤14, no differences in outcome were found between patients who underwent laparotomy within 60min of admission and those who underwent laparotomy within 60-120min of admission. In patients with blunt trauma, ISS ≥16, and GCS <15, mortality was higher in the immediate laparotomy group (p = 0.004 and 0.049, respectively). CONCLUSIONS: In patients with a penetrating injury, no differences in mortality between immediate and expedient laparotomy were demonstrated. In patients with a blunt injury, with ISS ≥16 and GCS <15, mortality was higher among the immediate laparotomy group.

Radiotherapy dose-distribution to the perirectal fat space (PRS) is related to gastrointestinal control-related complications.

Traditionally rectal symptoms following pelvic/prostate radiotherapy are correlated to the dosimetry of the anorectum or a substructure of this. It has been suggested that the perirectal fat space (PRS) surrounding the rectum may also be relevant. This study considers the delineation and dosimetry of the PRS related to both rectal bleeding and control-related toxicity. Initially, a case-control cohort of 100 patients from the RADAR study were chosen based on presence/absence of rectal control-related toxicity. Automated contouring was developed to delineate the PRS. 79 of the 100 auto-segmentations were considered successful. Balanced case-control cohorts were defined from these cases. Atlas of Complication Incidence (ACI) were generated to relate the DVH of the PRS with specific rectal symptoms; rectal bleeding and control-related symptoms (LENT/SOM). ACI demonstrated that control-related symptoms were related to the dose distribution to the PRS which was confirmed with Wilcoxon rank sum test (p < 0.05). To the authors knowledge this is the first study implicating the dose distribution to the PRS to the incidence of control-related symptoms of rectal toxicity.

Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population.

AIM: To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. METHODS AND MATERIALS: Population included 1336 patients, 3-year minimum follow-up, treated with 66-80Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ⩾2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. RESULTS: 4% of patients (45/1122) reported mean stool frequency grade >1; grade ⩾2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30-50Gy) for both endpoints. EUDs calculated with n=1 (OR=1.04) and n=0.35 (OR=1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR=1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR=4.2) for rectal pain. CONCLUSION: Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.

Two non-parametric methods for derivation of constraints from radiotherapy dose-histogram data.

Dose constraints based on histograms provide a convenient and widely-used method for informing and guiding radiotherapy treatment planning. Methods of derivation of such constraints are often poorly described. Two non-parametric methods for derivation of constraints are described and investigated in the context of determination of dose-specific cut-points-values of the free parameter (e.g., percentage volume of the irradiated organ) which best reflect resulting changes in complication incidence. A method based on receiver operating characteristic (ROC) analysis and one based on a maximally-selected standardized rank sum are described and compared using rectal toxicity data from a prostate radiotherapy trial. Multiple test corrections are applied using a free step-down resampling algorithm, which accounts for the large number of tests undertaken to search for optimal cut-points and the inherent correlation between dose-histogram points. Both methods provide consistent significant cut-point values, with the rank sum method displaying some sensitivity to the underlying data. The ROC method is simple to implement and can utilize a complication atlas, though an advantage of the rank sum method is the ability to incorporate all complication grades without the need for grade dichotomization.

Dosimetric intercomparison for multicenter clinical trials using a patient-based anatomic pelvic phantom.

PURPOSE: To assess dose delivery accuracy to clinically significant points in a realistic patient geometry for two separate pelvic radiotherapy scenarios. METHODS: An inhomogeneous pelvic phantom was transported to 36 radiotherapy centers in Australia and New Zealand. The phantom was treated according to Phase III rectal and prostate trial protocols. Point dose measurements were made with thermoluminescent dosimeters (TLDs) and an ionisation chamber. Comprehensive site-demographic, treatment planning, and physical data were collected for correlation with measurement outcomes. RESULTS: Dose delivery to the prescription point for the rectal treatment was consistent with planned dose (mean difference between planned and measured dose - 0.1 ± 0.3% std err). Dose delivery in the region of the sacral hollow was consistently higher than planned (+1.2 ± 0.2%). For the prostate treatment, dose delivery to the prostate volume was consistent with planned doses (-0.49 ± 0.2%) and planned dose uniformity, though with a tendency to underdose the PTV at the prostate-rectal border. Measured out-of-field doses were significantly higher than planned. CONCLUSIONS: A phantom based on realistic anatomy and heterogeneity can be used to comprehensively assess the influence of multiple aspects of the radiotherapy treatment process on dose delivery. The ability to verify dose delivery for two trials with a single phantom was advantageous.

Comparison of DVH data from multiple radiotherapy treatment planning systems.

This study examined the variation of dose-volume histogram (DVH) data sourced from multiple radiotherapy treatment planning systems (TPSs). Treatment plan exports were obtained from 33 Australian and New Zealand centres during a dosimetry study. Plan information, including DVH data, was exported from the TPS at each centre and reviewed in a digital review system (SWAN). The review system was then used to produce an independent calculation of DVH information for each delineated structure. The relationships between DVHs extracted from each TPS and independently calculated were examined, particularly in terms of the influence of CT scan slice and pixel widths, the resolution of dose calculation grids and the TPS manufacturer. Calculation of total volume and DVH data was consistent between SWAN and each TPS, with the small discrepancies found tending to increase with decreasing structure size. This was significantly influenced by the TPS model used to derive the data. For target structures covered with relatively uniform dose distributions, there was a significant difference between the minimum dose in each TPS-exported DVH and that calculated independently.

Comprehensive Australasian multicentre dosimetric intercomparison: issues, logistics and recommendations.

The present paper describes the logistics of the 2004-2008 Australasian Level III Dosimetry Intercomparison. Dosimetric intercomparisons (or 'audits') can be used in radiotherapy to evaluate the accuracy and quality of radiation delivery. An intercomparison was undertaken in New Zealand and Australia to evaluate the feasibility and logistics of ongoing dosimetric intercomparisons that evaluate all steps in the radiotherapy treatment process, known as a 'Level III' intercomparison. The study commenced in 2002 with the establishment of a study team, definition of the study protocol, acquisition of appropriate equipment and recruitment of participating radiotherapy centres. Measurements were undertaken between October 2004 and March 2008, and included collation of data on time, costs and logistics of the study. Forty independent Australian and New Zealand radiotherapy centres agreed to participate. Measurement visits were made to 37 of these centres. Data is presented on the costs of the study and the level of support required. The study involved the participation of 16 staff at the study centre who invested over 4000 hours in the study, and of over 200 professionals at participating centres. Recommendations are provided for future phantom-based intercomparisons. It is hoped that the present paper will be of benefit to any centres or groups contemplating similar activities by identifying the processes involved in establishing the study, the potential hazards and pitfalls, and expected resource requirements.

Surface laser scanning to routinely produce casts for patient immobilization during radiotherapy.

Immobilization casts are used to reduce patient movement during the radiotherapy of head and neck and brain malignancies. Polyethylene-based casts are produced by first taking a Plaster of Paris 'negative' impression of the patient. A 'positive' mould is then made, which is used to vacuum form an immobilization cast. Taking the 'negative' cast can be messy, stressful for patients and labour intensive. Recently, lightweight hand-held laser surface scanners have become available. These allow an accurate 3-D representation of objects to be generated non-invasively. This technology has now been applied to the production of casts for radiotherapy. Each patient's face and head is digitized using the Polhemus FastSCAN (Polhemus, Colchester, VT, USA) scanner. The electronic data are transferred to a computer numerical controlled mill, where a positive impression is machined. The feasibility of the process was examined, the labour required and radiation therapists' satisfaction with aspects of the produced masks assessed. The scanner-based method of mask production was found to be simple, accurate and non-invasive. There was a reduction in radiation therapist labour required. Masks produced with the scanner-based method were reported to result in improved mask fitting, daily reproducibility, patient immobilization and patient comfort.

Genetic counselling following paternal therapeutic irradiation.

We discuss a patient who received adjuvant radiotherapy for stage I seminoma. He was advised to avoid conception for 6 months following treatment. However, his partner became pregnant only shortly after he completed his radiotherapy (i.e. with sperm that had been irradiated). We estimated the dose received by the remaining testis as 30 cGy. Here, we review the information available to advise patients on the risks to the fetus from paternal preconception irradiation. For the population, a doubling dose for hereditary effects of 1 Gy has recently been reaffirmed (United Nations Scientific Committee on the Effects of Atomic Radiation 2001). However, a range of animal studies suggest conception with postmeiotic sperm carries a greater risk of genetic damage than conception with sperm derived from irradiated stem cells. We have attempted to quantify the risks in this particular case. Lead shielding of the testes may reduce radiation received from the primary beam, but internal scatter still produces a risk. In male patients who are potentially fertile, the best advice remains to delay conception after radiotherapy for as long as 6 months. Our case illustrates the need to reinforce such advice.

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia.

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p<0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p<0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p=0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p=0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes.

Functional similarities and differences of AMPA and kainate receptors expressed by cultured rat sensory neurons.

Dorsal root ganglion neurons express functional AMPA and kainate receptors near their central terminals. Activation of these receptors causes a decrease in glutamate release during action potential evoked synaptic transmission. Due to differences in kinetic properties and expression patterns of these two families of glutamate receptors in subpopulations of sensory neurons, AMPA and kainate receptors are expected to function differently. We used embryonic dorsal root ganglion (DRG) neurons maintained in culture to compare functional properties of kainate and AMPA receptors. Most DRG neurons in culture expressed kainate receptors and about half also expressed AMPA receptors. Most AMPA and kainate receptor-expressing DRG neurons were sensitive to capsaicin, suggesting involvement of these glutamate receptors in nociception. When activated by kainate, AMPA receptors were capable of driving a sustained train of action potentials while kainate receptors tended to activate action potential firing more transiently. Glutamate elicited more action potentials and a larger steady-state depolarization in neurons expressing both AMPA and kainate receptors than in neurons expressing only kainate receptors. Adding to their more potent activation properties, AMPA receptors recovered from desensitization much more quickly than kainate receptors. Activation of presynaptic receptors by low concentrations of kainate, but not ATPA, caused a tetrodotoxin-sensitive increase in the frequency of spontaneous EPSCs recorded in dorsal horn neurons. By recording synaptic pairs of DRG and dorsal horn neurons, we found that activation of presynaptic kainate and AMPA receptors decreased evoked glutamate release from terminals of DRG neurons in culture. Our data suggest that the endogenous ligand, glutamate, will cause a different physiological impact when activating these two types of non-NMDA glutamate receptors at central or peripheral nerve endings of sensory neurons.

Multicentre analysis of treatment planning information: technical requirements, possible applications and a proposal.

Digital data from 3-D treatment planning computers is generally used for patient planning and then never considered again. However, such data contains enormous quantities of information regarding patient geometries, tissue outlining, treatment approaches and dose distributions. Were such data accessible from planning systems from multiple manufacturers, there would be substantial opportunities for undertaking quality assurance of radiotherapy clinical trials, prospective assessment of trial outcomes and basic treatment planning research and development. The technicalities of data exchange between planning systems are outlined, and previous attempts at producing systems capable of viewing and/or manipulating imaging and radiotherapy digital data reviewed. Development of a software system for enhancing the quality of Australasian clinical trials is proposed.

A randomised trial of single-dose radiotherapy to prevent procedure tract metastasis by malignant mesothelioma.

A single 9-MeV electron treatment, following invasive thoracic procedures in patients with malignant pleural mesothelioma, was examined. In all, 58 sites were randomised to prophylactic radiotherapy or not. There was no statistically significant difference in tract metastasis. A single 10-Gy treatment with 9-MeV electrons appears ineffective.

A prospective trial of short-fractionation radiotherapy for the palliation of liver metastases.

The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty-eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty-two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high-dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53-66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well-tolerated treatment achieves useful palliation.

System validation and work practice efficiency gains of a new localization method for stereotactic radiotherapy.

The increased procedural demands of stereotactic localization techniques when compared with conventional treatment practices reduces machine efficiency, an outcome likely to be greatly magnified by the introduction of fractionation to stereotactic techniques. Currently in Australia and New Zealand there are no guidelines for the definition of efficiency. We sought to devise a system to simultaneously validate the accuracy and efficiency of the technique. The frameless relocation methods employed in the Medtronic Sofamor Danek (MSD) stereotactic radiotherapy (SRT) system were studied in the clinical setting. Accuracy has been determined according to the accumulation of errors throughout the planning and treatment process. The clinical demands of the system (staffing and resources) were analysed relative to conventional treatment approaches. Timing studies indicate a mean time of 19.7 min for treatment of a daily SRT fraction (4-5 arcs, single isocentre). Cost and staffing requirements are similar to those for conventional radiotherapy. It is concluded that with the system used, SRT is efficient for routine clinical implementation, with the level of efficiency increasing with increasing patient numbers. It is recommended that a common acceptance standard be developed to allow cross-institutional comparison of the clinical efficiency of new treatment techniques.

Introduction and implementation of the basic treatment equivalent in a Varian-based department.

The increasing popularity of 3-D planning leads to procedural alterations as both workload and resource utilization increase. Although the complexity of the techniques has increased (as well as the set-up and treatment times), the workload statistics must still include the number of fields treated. It is commonly known that machine statistics of fields treated per day do not accurately represent workload because there are major differences between techniques. A mantle treatment technique and an opposed spine technique both have (statistically) two fields, although the set-up requirements and treatment times are very different. A basic treatment equivalent (BTE) formula was reported in early 1999 by Delaney et al. and incorporates a large number of variables inherent in patient treatment. The formula considers different factors that affect overall treatment time, and aims to represent a more accurate treatment time indicator. The aim of introducing the BTE into the Department of Radiation Oncology at Sir Charles Gairdner Hospital was to create a more accurate scheduling system and even out workloads on all treatment units. Therefore the BTE formula was used to assess accuracy of treatment times in order to determine if the values could be relied upon as accurate time indicators. Patients undergoing a variety of treatment techniques were timed for the duration of their treatment procedure, and their treatment times compared to the time estimated using the BTE formula. A few minor alterations were made to the equation for treatment units with multi-leaf collimation (MLC). A trial conducted at Sir Charles Gairdner Hospital found that, using the BTE formula (with a few modifications required for the MLC treatment units), of 60 patients timed for the duration of their set-up and treatment, 85% of values were in the range of +/- 3 min, and 95% were in the range of +/- 5 min of the estimated times. Through the routine use of the BTE equation a more sensitive indication of treatment machine workload can be found. Advantages such as: (i) a more accurate measure of treatment workload (for comparison with other departments) and (ii) increased scheduling accuracy will succeed over the currently accepted system of fields per hour.