Retrospective Planning Study of Patients with Superior Sulcus Tumours Comparing Pencil Beam Scanning Protons to Volumetric-Modulated Arc Therapy.

AIMS: Twenty per cent of patients with non-small cell lung cancer present with stage III locally advanced disease. Precision radiotherapy with pencil beam scanning (PBS) protons may improve outcomes. However, stage III is a heterogeneous group and accounting for complex tumour motion is challenging. As yet, it remains unclear as to whom will benefit. In our retrospective planning study, we explored if patients with superior sulcus tumours (SSTs) are a select cohort who might benefit from this treatment. MATERIALS AND METHODS: Patients with SSTs treated with radical radiotherapy using four-dimensional planning computed tomography between 2010 and 2015 were identified. Tumour motion was assessed and excluded if greater than 5 mm. Photon volumetric-modulated arc therapy (VMAT) and PBS proton single-field optimisation plans, with and without inhomogeneity corrections, were generated retrospectively. Robustness analysis was assessed for VMAT and PBS plans involving: (i) 5 mm geometric uncertainty, with an additional 3.5% range uncertainty for proton plans; (ii) verification plans at maximal inhalation and exhalation. Comparative dosimetric and robustness analyses were carried out. RESULTS: Ten patients were suitable. The mean clinical target volume D95 was 98.1% ± 0.4 (97.5-98.8) and 98.4% ± 0.2 (98.1-98.9) for PBS and VMAT plans, respectively. All normal tissue tolerances were achieved. The same four PBS and VMAT plans failed robustness assessment. Inhomogeneity corrections minimally impacted proton plan robustness and made it worse in one case. The most important factor affecting target coverage and robustness was the clinical target volume entering the spinal canal. Proton plans significantly reduced the mean lung dose (by 21.9%), lung V5, V10, V20 (by 47.9%, 36.4%, 12.1%, respectively), mean heart dose (by 21.4%) and thoracic vertebra dose (by 29.2%) (P < 0.05). CONCLUSIONS: In this planning study, robust PBS plans were achievable in carefully selected patients. Considerable dose reductions to the lung, heart and thoracic vertebra were possible without compromising target coverage. Sparing these lymphopenia-related organs may be particularly important in this era of immunotherapy.

Trans sodium crocetinate for hemorrhagic shock: effect of time delay in initiating therapy.

A new drug, trans sodium crocetinate (TSC), has been suggested for use in resuscitation after trauma. TSC has been shown to increase survival in a rat model of hemorrhagic shock. It also results in an increase in blood pressure and a decrease in plasma lactate levels when given immediately after hemorrhage. TSC increases whole-body oxygen consumption rates, and it is thought that its physiological effects are due to the increased oxygen availability. In fact, TSC therapy and 100% oxygen therapy show similar results when used in the same rat hemorrhage model. It has been suggested, however, that 100% oxygen therapy is effective only if begun immediately after hemorrhage. Such a window of opportunity has been said to exist for other resuscitation methods; thus, the current study is to determine if this is true for TSC. In one series of experiments, rats were bled 60% of their blood volumes and given an injection of TSC (or saline) 20 min after the hemorrhage ended. The injection was then repeated four times, spaced 10 min apart. Thirty minutes after the final injection, the animals were infused with normal saline. TSC again restored blood pressure and other parameters, but repeated dosing was necessary. In addition, this therapy prevented an increase in liver enzymes (transaminases) as measured 24 h after hemorrhage. In a second study, rats were bled 60% of their blood volumes, followed by a second bleeding (an additional 10%) done 10 min later. No subsequent fluid was infused in this group. The majority of the animals treated with TSC after the second hemorrhage survived, whereas the controls did not. These data suggest that TSC is effective when given after a delay. The dosing regimen must be different, however, presumably because of the blood acidosis that develops after hemorrhage. The results also suggest that TSC may be protective against secondary liver damage resulting from trauma.

Normal lung growth following antenatal dexamethasone treatment for respiratory distress syndrome.

Antenatal steroid therapy reduces the incidence of respiratory distress syndrome (RDS) in premature infants. However, animal studies showed a decrease in lung cell number and lower lung weights in fetal rabbits exposed to hydrocortisone. This prompted us to measure flows and lung volumes (by spirometry and helium-dilution method) in children greater than 6 years who were part of a study by the Collaborative Group on Antenatal Steroid Therapy. The effect of antenatal steroids on subsequent pulmonary function had not previously been studied. Of the 158 children originally enrolled before birth, a total of 8 dexamethasone (DEX)- and 11 placebo-treated children were still local residents and fulfilled the criteria of the study (gestational age, 28-34 weeks; DEX/placebo treatment 1-7 days before delivery). Mean heights and weights were normal with no significant differences between the groups. Pulmonary function tests showed no differences in lung volumes or expiratory flows between the children whose mothers had received antenatal DEX and those who had received placebo. These results indicate no adverse effect of antenatal DEX on subsequent lung volumes and expiratory flows in childhood.

Effect of terfenadine on the response to exercise and cold air in asthma.

To assess the role of histamine as a mediator in the response to exercise and isocapnic hyperventilation of cold air (IHCA) in asthma, we studied nine asthmatic subjects, age 13 to 25 years. All had exercise induced asthma (EIA) and positive responses to IHCA. Baseline lung function was measured before standardized challenges with histamine, exercise and IHCA. On separate days, these tests were repeated 3 h after a single oral dose of 120 mg terfenadine (TF). Histamine responsiveness decreased significantly, with a provocative concentration, producing a greater than or equal to 20% fall in FEV1 (PC20), of 1.1 +/- 0.8 mg/ml (mean +/- SEM) before and 12.0 +/- 4.9 mg/ml after the antihistamine. EIA was significantly less after TF, with 53 +/- 5% mean maximal falls in FEV1 from baseline before, and 29 +/- 9% after treatment (P less than 0.01, paired t-test). In contrast, the effect of TF on the response to IHCA was insignificant, with mean maximal falls of 45 +/- 7% in FEV1 before, and 41 +/- 7% after treatment. There was a correlation between PC20 and lowest FEV1 (% predicted) for EIA (r = 0.56, P less than 0.05), but not for IHCA (r = 0.34, NS). This study indicates a role of histamine as a mediator in EIA but not in IHCA, supporting different mechanisms for both stimuli.

Direct measurement of air kerma rate in air from CDCS J-type caesium-137 therapy sources using a Farmer ionization chamber.

A simple method for directly measuring the reference air kerma rate from J-type 137Cs sources using a Farmer 2571 chamber has been evaluated. The method is useful as an independent means of verifying manufacturers' test data.

Image quality parameters for the production standard Eliav PORTpro portal imaging device.

Measurements of the high contrast spatial resolution and contrast-to-noise ratio of the production standard Eliav "PORTpro" portal imaging system have been made using a commercially available quality assurance phantom. The spatial resolution of the images is comparable with published data for other commercial systems, but somewhat lower than that published previously for the prototype of this system. These data may be of use to those involved in the selection, commissioning or quality assurance testing of electronic portal imaging systems.

Practical experience with intensity-modulated radiotherapy.

At the Ipswich Hospital implementation of intensity-modulated radiotherapy (IMRT) commenced in February 2001 based on an established 3D conformal radiotherapy (3D CRT) service. This paper describes our experiences as we commissioned a fully-integrated IMRT planning and delivery system, and established IMRT within the department. Commissioning measurements incorporated a series of tests to ensure the integrity of the system and form the basis of routine quality assurance (QA) procedures. Potential IMRT patients proceeded through pre-treatment in the same way as standard 3D CRT patients. All were dual-planned for IMRT and 3D CRT with no change in established fractionation regimen, and the resulting plans evaluated. IMRT was selected for treatment where it offered a significant advantage by improving dose homogeneity and conformity within the target volume and/or reducing dose to organs at risk. Extensive pre-treatment verification was undertaken on all plans to check dynamic multileaf collimator (MLC) delivery and monitor unit calculation. Patients were monitored throughout treatment with amorphous silicon electronic portal imaging to ensure reproducibility of set-up. Between June 2001 and June 2003 21 patients were treated with inverse-planned IMRT to sites within the head and neck and lung. IMRT has enabled precise delivery to irregular shaped target volumes, avoiding organs at risk and enabling doses to be increased to radical levels in some cases. Additionally over 200 CT scanned breast patients were treated with forward-planned electronic compensation delivered by dynamic MLC, improving dose homogeneity within the breast volume compared with standard wedged plans. The IMRT programme will continue at the Ipswich Hospital with the introduction of further clinical sites and adoption of more aggressive fractionation regimens within the confines of multicentre clinical trials.

The driniking driver: a blueprint for some further action.

Statistical information relating to the offence of drunken driving in New Zealand is reviewed. The relationship between alcoholism and this offence is discussed. Two groups of offenders who should be dealt with separately can be identified. A plan is put forward with an outline of methods which could be used for dealing with this problem.

Image-guided radiotherapy of the prostate using daily CBCT: the feasibility and likely benefit of implementing a margin reduction.

OBJECTIVE: To investigate whether planning target volume (PTV) margins may be safely reduced in radiotherapy of localized prostate cancer incorporating daily online tube potential-cone beam CT (CBCT) image guidance and the anticipated benefit in predicted rectal toxicity. METHODS: The prostate-only clinical target volume (CTV2) and rectum were delineated on 1 pre-treatment CBCT each week in 18 randomly selected patients. By transposing these contours onto the original plan, dose-volume histograms (DVHs) for CTV2 and the rectum were each calculated and combined, for each patient, to produce a single mean DVH representative of the dose delivered over the treatment course. Plans were reoptimized using reduced CTV2 to PTV2 margins and the consequent radiobiological impact modelled by the tumour control probability (TCP) and normal tissue complication probability (NTCP) of the rectum. RESULTS: All CBCT images were deemed of sufficient quality to identify the CTV and rectum. No loss of TCP was observed when plans using the standard 5-mm CTV2 to PTV2 margin of the centre were reoptimized with a 4- or 3-mm margin. Margin reduction was associated with a significant decrease in rectal NTCP (5-4 mm; p < 0.05 and 5-3 mm; p < 0.01). CONCLUSION: Using daily online image guidance with CBCT, a reduction in CTV2 to PTV2 margins to 3 mm is achievable without compromising tumour control. The consequent sparing of surrounding normal tissues is associated with reduced anticipated rectal toxicity. ADVANCES IN KNOWLEDGE: Margin reduction is feasible and potentially beneficial. Centres with image-guided radiotherapy capability should consider assessing whether margin reduction is possible within their institutes.

UK guidelines for the safe delivery of intensity-modulated radiotherapy.

This paper outlines the guidelines for the development of intensity-modulated radiotherapy (IMRT) in the UK. The guidelines are designed to cover the complete implementation of IMRT, with guidelines in the following categories: commissioning, quality, clinical, audit, and training and education. These guidelines have been compiled by the Radiotherapy Development Board of the Royal College of Radiologists and will support the safe application of IMRT in the UK.

A multicentre timing study of intensity-modulated radiotherapy planning and delivery.

AIMS: The aim of the study was to measure how long the intensity-modulated radiotherapy (IMRT) process takes, both for planning and delivery, using several IMRT techniques and departments. MATERIALS AND METHODS: Timings were measured at three radiotherapy centres for each step of the process of outlining, planning and delivering IMRT for head and neck cancers. Times were measured for a total of 63 patients; 27 with helical tomotherapy, 37 with dynamic sliding window (26 in one centre, 11 in another) and nine with step-and-shoot. RESULTS: The mean time to outline a patient was 108 min, to produce and check the plan 7.9 h, to carry out and analyse patient-specific quality assurance 1.9 h. The mean treatment time (including on-treatment verification imaging where carried out), measured gate to gate, was 28 min 10 s for first fractions and 20 min 20 s for subsequent fractions. CONCLUSION: An analysis of subgroups showed some differences in times between techniques, and some differences between departments with the same techniques. For all four techniques, the median time from the end of outlining to the start of treatment was under 3 weeks.

[The effect of ipratropium bromide on lung function in patients with cystic fibrosis]. / Der Einfluss von Ipratropiumbromid auf die Lungenfunktion bei Patienten mit zystischer Fibrose.

The main manifestation of cystic fibrosis (CF) of the lungs is an obstructive ventilation disturbance. The fact that the administration of atropine improves pulmonary function in patients with CF suggests a vagal mechanism for the development of bronchal obstruction. In a single-blind, placebo-controlled study, we investigated the effect of 250 micrograms of an inhalation solution of the anticholinergic substance ipatropium bromide (IB) on the pulmonary function of 11 patients with CF (age range: 8 to 29 years). The mean figures for the changes in FEV1.0, FEF25-75%, RV and TLC after inhalation of IB and placebo did not differ significantly. However, FEV1.0 and FEF25-75% after administration of IB increased in 4 out of 11 patients, and decreased in one. The lung volumes changed significantly in only a single case. This variable effect of inhaled IB in CF patients is in agreement with findings that have been observed for other substances with a "bronchodilatory" effect in patients with CF.