Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated ...stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer.
PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0–2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1–2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing.
Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference −1·9 percentage points, 95% CI −6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference −4·2 percentage points, 95% CI −10·0 to 1·7; p=0·16). No treatment-related deaths occurred.
Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity.
Accuray and National Institute of Health Research.
Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter ...treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT.
PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0–2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1–2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258.
We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% 95% CI –1·3 to 4·0; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference –1·3% 95% CI –3·9 to 1·1; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe.
In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited.
Accuray.
To analyse outcomes in metastatic castrate-resistant prostate cancer (mCRPC) patients treated with radium 223 (Ra-223) across the Yorkshire and Humber Cancer Network.
A regional, multicentre, ...retrospective cohort study of 189 men undergoing Ra-223 for mCRPC between March 2014 and April 2017 was undertaken. Factors predicting overall survival and completion of planned treatment were assessed.
The median overall survival for the entire cohort was 10.5 months. Those completing five to six cycles of Ra-223 had a higher overall survival of 18.6 months. On multivariable analysis, four factors remained independent significant predictors of overall survival: age (P = 0.005, hazard ratio 1.07 1.02–1.12); number of cycles of Ra-223: 5–6 versus 1–4 (P ≤ 0.001, hazard ratio 0.10 0.005–0.20); baseline alkaline phosphatase (P = 0.044, hazard ratio 1.06 1.002–1.12); neutrophil-to-lymphocyte ratio (P = 0.033, hazard ratio 1.19 1.01–1.40). Baseline performance status 0 versus 2 (P = 0.026, odds ratio 0.080 0.001–0.74) and higher baseline haemoglobin (P = 0.028, odds ratio 1.04 1.004–1.074) were independent predictors of the completion of five to six cycles of Ra-223.
Younger age, completion of five to six cycles of Ra-223, lower alkaline phosphatase and neutrophil-to-lymphocyte ratio are predictors of overall survival. This is the first study to report neutrophil-to-lymphocyte ratio as an independent predictor of overall survival in a Ra-223 cohort. Good performance status and higher baseline haemoglobin predict the completion of five to six cycles of Ra-223.
•Regional audit of recently introduced radium 223 service shows survival outcomes similar to previously published.•Good performance state and nearer normal haemoglobin predict likelihood of completing planned treatment.•Neutrophil-to-lymphocyte ratio is an independent predictor of survival.
Despite the breast being a mobile organ, there is currently no standard suitable immobilisation device to optimise radiotherapy for women with larger breasts treated after a wide local excision. The ...SuPPORT 4 All (S4A) bra was co-designed with patients and radiotherapy professionals. The purpose of this study was to test the feasibility of using the S4A bra in the existing breast cancer radiotherapy pathway.
A randomised feasibility trial was conducted in a single institution; the primary feasibility endpoint was the recruitment of 50 participants. Efficacy endpoints were also tested, including assessment of skin reactions, dose to organs at risk and patient comfort. Fifty women were randomised to receive either standard radiotherapy with no immobilisation (control) or radiotherapy with the S4A bra (intervention). A separate planning study was undertaken on the cases randomised to receive the S4A bra. Participants in the intervention arm (S4A bra) underwent two planning computed tomography scans, one with the bra on and one without the bra; allowing direct comparison of organs at risk data for S4A bra versus no bra.
All women who started radiotherapy wearing the S4A bra completed treatment with the bra; patient comfort did not change across the 3 weeks of treatment. Positional accuracy using the bra was comparable with existing published accuracy for methods without immobilisation. The mean ipsilateral lung doses showed some improvement when positioning with the S4A bra was compared with the no bra set-up (3.72 Gy versus 4.85 Gy for right-sided cases, 3.23 Gy versus 3.62 Gy for left-sided cases).
The S4A bra is feasible to use in the radiotherapy pathway with good patient adherence. The S4A bra has potential to reduce dose to organs at risk (specifically ipsilateral lung dose) while maintaining good breast tissue coverage, and improved patient dignity, warranting further investigation on a larger scale.
Background
Fish, a widely claimed healthy food for humans, could also pose problems to health due to accumulation of pollutants, especially heavy metals and pesticides. Since the world’s fish stocks ...are limited due to overfishing, degraded freshwater, and pollution from various sources, the government proposed farmed fish which is one of the fastest growing food production sectors as an alternative.
The objective of this study was to investigate the effects of tilapia or
Mugil cephalus
fish diets obtained from polluted areas on male reproductive hormones and prolactin. A total of 80 male Wister albino rats having an average weight of 130–150 g at the beginning of the experiment were used. They were divided into control group and seven treated groups which received the following doses that increased monthly according to the increase in rat body weight (b.w.). The treated groups received 200 g/70 kg human b.w. which is equivalent to 0.4 g/140 g rat b.w., 0.63 g/220 g rat b.w., and 0.83 g/291 g rat b.w. of tilapia fish (wild and farmed freshwater and brackish water) or
Mugil cephalus
fish (farmed freshwater and brackish water and wild marine water) daily for 3 months then were left on AIN-93M diet and purified water ad libitum.
Results
The present results demonstrated that tilapia and
Mugil cephalus
fish diets caused decrease in serum total testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count, while sperm abnormalities significantly increased. Also, significant elevation of serum prolactin was observed in male rats fed with the same diets except wild brackish water tilapia fish and farmed freshwater and brackish water
Mugil cephalus
fish diets which showed a decrease. However, tilapia and
Mugil cephalus
fish diets had no effect on serum 17β-estradiol. The histopathological studies confirmed biochemical data as less dense packing of spermatogenic cell of the seminiferous tubules with reduction in the number of sperms in lumen of the epididymal tubules.
Conclusions
These results may indicate that consumption of tilapia and
Mugil cephalus
fish diets from polluted areas has adverse effects on male reproductive hormones and prolactin in male albino rats.
Abstract Aims Aromatase inhibitors are now a standard of care in the management of hormone-responsive early breast cancer in postmenopausal women. The troublesome side-effect of arthralgia remains a ...distinct clinical problem, with limited data on its aetiology and management. The aim of this questionnaire study was to evaluate the opinion of UK breast cancer clinicians on the importance of this treatment side effect. Materials and methods In 2009, a questionnaire was sent to 772 breast surgeons and oncologists who manage breast cancer within the UK. The questionnaire evaluated the importance, investigation, management and the need for guidelines for aromatase inhibitor-induced arthralgia (AIA). Results Four hundred and sixteen (54%) returned questionnaires were suitable for analysis. By specialty, 234 (56%) were completed by breast surgeons, 134 (32%) by clinical oncologists, 45 (11%) by medical oncologists and one by a general surgeon. Three hundred and eighty-three (92%) specialists graded the importance of AIA as either very important or important; 211 (51%) did not know the aetiology of AIA; 280 (68%) did not perform bloods; 254 (61%) did not request radiology and 251 (60%) felt management was the responsibility of the oncologists. Three hundred and forty-nine (84%) considered that their practice would benefit from national guidelines. Conclusion This questionnaire has highlighted that AIA is a major patient concern. Further research, educational initiatives and guidance are needed to improve the management of this treatment complication.
Abstract Aims A variety of radical radiotherapy regimens are in use for non-small cell lung cancer. Continuous hyperfractionated accelerated radiotherapy (CHART: 54 Gy in 36 fractions over 12 days) ...and accelerated hypofractionated radiotherapy using 55 Gy in 20 fractions over 4 weeks are standard fractionations in our centre. The primary aim of this retrospective study was to evaluate survival outcome seen in routine clinical practice. Materials and methods All case notes and radiotherapy records of radically treated patients between 1999 and 2004 were retrospectively reviewed. Basic patient demographics, tumours, characteristics, radiotherapy and survival data were collected. Results In total, 277 patients received radical radiotherapy: 137 and 140 patients received CHART and hypofractionated radiotherapy, respectively. There were differences noted in the demographics between the two treatment schedules: median age 65 years (range 41–83) vs 73 years (range 33–87); histological confirmation rates 90% vs 76%; prior chemotherapy 34% vs 19% for CHART and hypofractionated treatment, respectively. For CHART patients, stages I, II, III and unclassified were 12, 8, 68 and 12% and the staging for the hypofractionated regimen was 54, 11, 34 and 2%, respectively. The median overall survival from the time of diagnosis was 20.4 months with a 40% 2-year survival rate. For the two fractionations the median survival was 16.6 months vs 21.4 months and 34% vs 45% of patients were alive at 2 years in the CHART and hypofractionated groups, respectively. On multivariate analysis, stage was the only factor affecting overall survival — no difference was seen according to radiotherapy regimen. Conclusion This single-centre study reflects the outcome of unselected consecutively treated non-small cell lung cancer patients. Adjusting for stage, there was no significant difference in survival seen according to regimen. Encouragingly, CHART outcome shows reproducibility with the original CHART paper. Our hypofractionated outcome is similar to that previously reported, but despite this being the UK's most common regimen, 55 Gy in 20 daily fractions remains unvalidated by phase III trial data.
Using solvent extraction, we studied the oil refining process of diesel fuel fraction (boiling range 212°C to 343°C) crude oil from the Suez oil petroleum company (Cairo, Egypt). We used organic ...solvents such as dimethylsulfoxide (DMSO), furfural, mixtures of N-methylpyrrolidone (NMP) + ethylene glycol (EG) as an antisolvent as well as dimethylformamide (DMF) + (EG). In addition, we determined the critical solution temperature (CST) of the examined solvents with the feedstock. The efficiency of pure and mixed solvents has been evaluated in terms of yield and characteristics of the raffinates obtained. We evaluated the selectivity (β) as well as the solvent power (K) of the examined solvents. The ternary miscibility diagrams of the systems' diesel fuel fraction (pure and mixed solvents) have also been determined.
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