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

Background 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. Methods 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. Findings 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. Interpretation 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

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

Background 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. Methods 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 . Findings 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. Interpretation 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. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

The effect of a structured exercise program on fatigue, strength, endurance, physical self -efficacy, and functional wellness in women with early stage breast cancer.

Cancer treatment-related fatigue is a distressing effect of cancer therapy. Early efforts in describing the fatigue experience have progressed to the testing of potential interventions. This study built on the fatigue, functional capacity, and exercise activity of previous studies with women with early stage breast cancer. Strength training and the nature of the relationship of physical self-efficacy and performance to functional wellness, contribute new understanding to the area of fatigue and symptom management. The purpose of this thirteen-week study was to test the effectiveness of a structured exercise program in decreasing fatigue, increasing physical performance, increasing perceptions of attention performance and physical self-efficacy, and enhancing perceptions of functional wellness in women undergoing a specific type of adjuvant chemotherapy for early stage breast cancer. The study utilized a randomized, two-group, repeated measures experimental design. The sample consisted of 22 women (36--58 years) randomized to comparison (n = 9) and intervention (n = 13) groups. Both groups were tested at weeks 1 and 13 for physical performance (VO2max and 1-Repetition Maximum) and attention performance (Attention Functional Index). Measurement of fatigue (Revised Piper Fatigue Scale), physical self-efficacy (Physical Self-Efficacy Scales), and functional wellness (MOS SF-36, and Functional Wellness Questionnaire) occurred during weeks l, 7, and 13. Data analysis found significant differences between groups in VO2max from weeks 1 to 13. Significant differences in activity also existed between the two groups. Treatment-related fatigue increased over the study period for both groups, although the intervention group reported lower overall fatigue scores, as compared to the comparison group. Perceptions of physical self-efficacy declined in both groups over the study period with the peak fall at week 7, the midpoint of the study. Preliminary testing of the proposed conceptual model utilizing multiple regression, demonstrated support for relationships between dose, exercise program, performance, physical self-efficacy, functional wellness, and fatigue. Correlation coefficients strongly supported the associations between fatigue and vitality, physical self-efficacy with attention performance, attention performance with vitality, and physical self-efficacy and physical functioning. These findings, provide support to the positive role of exercise during a specific type of adjuvant chemotherapy for early stage breast cancer.Ph.D.Health and Environmental SciencesNursingPublic healthUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/123815/2/3106039.pd

Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease

Edificio de uso mixto en la High Line. Manhattan. New York. Convocatoria Abril. Plan 1996. Proyecto fin de carrera. Universidad Politécnica de Madrid. Escuela Técnica Superior de Arquitectur

Administration of depot and long-acting antipsychotic injections

It is essential for healthcare professionals to share good practice and information in partnership with those who use health and social care services (National Institute for Mental Health in England 2008). The aim of this guide is to inform all practitioners, managers, service users and carers about the use of intramuscular (IM) depot and long-acting injectable (LAI) antipsychotic medication. The recognition of service users’ need for privacy, safety and dignity when receiving these injections will be emphasised