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result(s) for
"Lees, Laura"
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Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
by
Pascoe, Caitlin
,
Lemng Kruse, Helle
,
Livsey, Jacqueline
in
Aged
,
Androgen Antagonists - administration & dosage
,
Androgen Antagonists - therapeutic use
2024
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Journal Article
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
by
Pascoe, Caitlin
,
Lemng Kruse, Helle
,
Livsey, Jacqueline
in
Aged
,
Androgen Antagonists - administration & dosage
,
Androgen Antagonists - therapeutic use
2024
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Journal Article
The role of the ‘on treatment’ review radiographer: what are the requirements?
2008
Purpose: The aims of this study were to describe the scope of practice of the radiotherapy ’on treatment’ review radiographer. This included trying to gain an insight in to what knowledge, skills and characteristics are needed to operate in this role extension and to establish whether the role requires skills in areas of patient care and support which are beyond the generic training of a treatment floor therapy radiographer. Method: A qualitative grounded theory methodology was employed using semi-structured interviews with ’on treatment’ review radiographers from three different departments. The departments were selected to maximise the amount of data collected, consequently they were chosen due to the differences in the way their review service was set up. This ranged from full time, to team led, to part time review. Using coding and constant comparative analysis based on grounded theory, categories were developed describing attributes of the role. Results: The scope of practice and challenges of the role varied slightly between the departments. The core categories needed to operate in the role were identified as knowledge, listening skills and characteristics with sub categories of self-reflection, interpersonal skills and attitudes. Conclusions: To be a review radiographer requires advanced knowledge at Masters level, with well developed listening and interpersonal skills and enjoyment of the people side of the profession. These skills need to be regularly practised, updated and reflected upon. The requirements for further training needs are noted and recommendations for further research are identified along with the limitations of this research. The role appears to require knowledge and skills in areas of patient care and support, which are above the level of practice of a treatment floor therapy radiographer.
Journal Article
Establishing a large prospective clinical cohort in people with head and neck cancer as a biomedical resource: head and neck 5000
by
Leary, Sam
,
Hollingworth, Will
,
Ness, Andrew Robert
in
Biomedical and Life Sciences
,
Biomedical research
,
Biomedicine
2014
Background
Head and neck cancer is an important cause of ill health. Survival appears to be improving but the reasons for this are unclear. They could include evolving aetiology, modifications in care, improvements in treatment or changes in lifestyle behaviour. Observational studies are required to explore survival trends and identify outcome predictors.
Methods
We are identifying people with a new diagnosis of head and neck cancer. We obtain consent that includes agreement to collect longitudinal data, store samples and record linkage. Prior to treatment we give participants three questionnaires on health and lifestyle, quality of life and sexual history. We collect blood and saliva samples, complete a clinical data capture form and request a formalin fixed tissue sample. At four and twelve months we complete further data capture forms and send participants further quality of life questionnaires.
Discussion
This large clinical cohort of people with head and neck cancer brings together clinical data, patient-reported outcomes and biological samples in a single co-ordinated resource for translational and prognostic research.
Journal Article
Executives Face 'Burnout'
by
Lees, Laura
1983
ST. LOUIS -- As the nation's corporate leaders come to depend more on computers and less on human interaction in the workplace, \"executive burnout\" will become more commonplace.
Newspaper Article
'I am horrified ... the funeral that my sister went through was everything we didn't want to happen'
2002
When funeral directors Green Willows went to collect her body from Llandough Hospital on Monday, they discovered she was not there. Lucy Davies, spokeswoman for the Funeral Standards Council, based in Cardiff, said: \"Instances of the wrong body being cremated or buried are very rare. There are strict procedures for both hospital mortuaries and funeral directors before a body is released. SHOCKED Liz RobertsMorgan's twin sister [Mary Williams], inset, was mistakenly cremated. MAIN PICTURE:Simon Ridgway; MIX UP Llandough Hospital.
Newspaper Article
A stormy outlook for fans on way to Dublin
THE forecast is bleak for thousands of rugby fans trying to get to Dublin to see the Wales team take on Ireland in the opening Six Nations clash this weekend. He said Irish Ferries is planning to take 5,000 fans over to Ireland and about 1,300 would be diverted to Holyhead from Pembroke. Firm partner Jason Ferris said: \"Our customers are due to sail from [Holyhead Coastguard] to Dublin with Irish Ferries.
Newspaper Article
An African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation
2019
Bloodstream infections by
Salmonella enterica
serovar Typhimurium constitute a major health burden in sub-Saharan Africa (SSA). These invasive non-typhoidal (iNTS) infections are dominated by isolates of the antibiotic resistance-associated sequence type (ST) 313. Here, we report emergence of ST313 sublineage II.1 in the Democratic Republic of the Congo. Sublineage II.1 exhibits extensive drug resistance, involving a combination of multidrug resistance, extended spectrum β-lactamase production and azithromycin resistance. ST313 lineage II.1 isolates harbour an IncHI2 plasmid we name pSTm-ST313-II.1, with one isolate also exhibiting decreased ciprofloxacin susceptibility. Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity. Sublineage II.1 emerged at the beginning of the 21st century and is involved in on-going outbreaks. Our data provide evidence of further evolution within the ST313 clade associated with iNTS in SSA.
Invasive non-typhoidal
Salmonella
(iNTS) infections are dominated by antibiotic resistant isolates of the sequence type (ST) 313. Here, the authors identify the ST313 sublineage II.1 in the Democratic Republic of the Congo exhibiting extensive drug resistance and genetic signatures potentially associated with host adaptation.
Journal Article
Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis
by
Derikx, Lauranne A.A.P.
,
Siakavellas, Spyros
,
Jones, Gareth-Rhys
in
Clinical trials
,
Colorectal surgery
,
Gastroenterology
2021
Background and aims:
Tofacitinib is a Janus kinase inhibitor (JAKi) recently approved for the treatment of moderate to severe ulcerative colitis (UC) based on robust efficacy and safety data derived from OCTAVE clinical trials. Evidence on the outcomes of tofacitinib therapy in real-world UC patients is needed, as a number of these patients would be deemed ineligible for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe UC patients.
Methods:
We searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30 May 2018 and 24 January 2021. Pooled induction (8–14 weeks) and maintenance (16–26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models.
Results:
Nine studies were included, comprising 830 patients, of which 81% were previously treated with anti-tumour necrosis factor (TNF) and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% confidence interval, 41–60%) and 37% (26–45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31–50%) and 29% (23–36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%).
Conclusion:
Tofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials.
Journal Article