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

Professional learning in different contexts of mathematics teacher education

Editoria

The role of professional development in using calculators in a sample of Queensland primary schools

A survey ascertained teachers' knowledge about and use of hand-held calculators in primary mathematics classes. This paper focuses on 341 teachers' experiences of Professional Development(PD) on the use of calculators in teaching mathematics. Only nine had experienced such a workshop in the past two years while 10% had during their career. Approximately 40% regarded themselves as poorly prepared for calculator use in their teaching. A face-to-face hands-on PD session conducted by an 'expert' was the teachers' choice to develop their calculator pedagogy

Mental models of the teaching and learning with the www

Mental models are deeply ingrained assumptions or generalisations that are continuously being processed for each situation. The roots of success or failure are linked to mental models which profoundly influence how and why we act. Yet there is insubstantial research concerning the use of mental models in teaching and learning, especially with the Internet. The paper aims to inform our (mis)understanding of the multiplicity of mental models held b)' Master of Education distance education students. The paper analyses the students' mental models prior to (espoused stage), and at the end of the course (reflectivity stage). There were significant changes to the students' mental models concerning learning and teaching with the WWW. The course and its assessment were instrumental change agents. The pedagogies allowed in their workplaces were also a significant factor

Mental models of the teaching and learning with the www

Mental models are deeply ingrained assumptions or generalisations that are continuously being processed for each situation. The roots of success or failure are linked to mental models which profoundly influence how and why we act. Yet there is insubstantial research concerning the use of mental models in teaching and learning, especially with the Internet. The paper aims to inform our (mis)understanding of the multiplicity of mental models held b)' Master of Education distance education students. The paper analyses the students' mental models prior to (espoused stage), and at the end of the course (reflectivity stage). There were significant changes to the students' mental models concerning learning and teaching with the WWW. The course and its assessment were instrumental change agents. The pedagogies allowed in their workplaces were also a significant factor

MENTAL MODELS OF TEACHING AND LEARNING WITH THE WWW

Mental models are deeply ingrained assumptions or generalisations that are continuously being processed for each situation. The roots of success or failure are linked to mental models which profoundly influence how and why we act. Yet there is insubstantial research concerning the use of mental models in teaching and learning, especially with the Internet. The paper aims to inform our (mis)understanding of the multiplicity of mental models held by Master of Education distance education students. The paper analyses the students ’ mental models prior to (espoused stage), and at the end of, the course (reflectivity stage). There were significant changes to the students ’ mental models concerning learning and teaching with the WWW. The course and its assessment were instrumental change agents. The pedagogies allowed in their workplaces were also a significant factor

Primary school students' statistical thinking: a comparison of two australian states

A framework for teaching and assessing statistical thinking comprising four constructs and four levels for each construct, has been developed and the framework validated using data from 20 US students in Years 1 - 5. The same validation· procedures· were implemented in two different cohorts, totalling 40 subjects, of Australian students in Years 1 - 5. Lower levels of coherence were found. This paper reports the Australian data, seeks to address reasons for the differences and compares the levels of performance between the Australian and US students

Catering for exceptional students in mathematics

Recently, there has been considerable attention to the development of the mathematical capability of Australasian citizens. It is widely accepted that all citizens should be numerate. That is, they should be able to cope with the everyday mathematical demands of life at school, in the home, at work, and in the community. Additionally, there is a need for adequate numbers of citizens to develop the high-level mathematical capability necessary to support and advance our technologically-oriented society (Howard, 2001; MacGillivray, 2000). Thus, the dual goals of contemporary mathematics education are (1) to develop a numerate citizenry, and (2) to develop a society with sufficient high-level mathematical capability. However, to achieve these goals, we must understand how to adequately cater for exceptional students, such as those who have learning difficulties and those who are gifted in mathematics. While students with learning difficulties and gifted students clearly differ substantively, they are both "at risk" of underachieving in mathematics (Diezmann, Thornton, & Watters, 2003). This chapter provides an overview of the context for the education of students with learning difficulties and mathematically gifted students, reviews the associated research, and suggests avenues for future mathematics education research to support exceptional students