An objective measure of response on whole-body MRI in metastatic hormone sensitive prostate cancer treated with androgen deprivation therapy, external beam radiotherapy, and radium-223.

OBJECTIVES: The aim of this study was to generate an objective method to describe MRI data to assess response in the vertebrae of patients with metastatic hormone sensitive prostate cancer (mHSPC), treated with external beam radiation therapy and systemic therapy with Radium-223 and to correlate changes with clinical outcomes. METHODS: Three sets of whole-body MRI (WBMRI) images were utilized from 25 patients from the neo-adjuvant Androgen Deprivation Therapy pelvic Radiotherapy and RADium-223 (ADRRAD) clinical trial: MRI1 (up to 28 days before Radium-223), MRI2, and MRI3 (2 and 6 months post completion of Radium-223). Radiological response was assessed based on post baseline MRI images. Vertebrae were semi-automatically contoured in the sagittal T1-weighted (T1w) acquisitions, MRI intensity was measured, and spinal cord was used to normalize the measurements. The relationship between MRI intensity vs time to biochemical progression and radiology response was investigated. Survival curves were generated and splitting measures for survival and biochemical progression investigated. RESULTS: Using a splitting measure of 1.8, MRI1 was found to be a reliable quantitative indicator correlating with overall survival (P = 0.023) and biochemical progression (P = 0.014). MRI (3-1) and MRI (3-2) were found to be significant indicators for patients characterized by progressive/non-progressive disease (P = 0.021, P = 0.004) and biochemical progression within/after 12 months (P = 0.007, P = 0.001). CONCLUSIONS: We have identified a potentially useful objective measure of response on WBMRI of vertebrae containing bone metastases in mHSPC which correlates with survival/progression (prognostic) and radiology response (predictive). ADVANCES IN KNOWLEDGE: Measurements of T1w WBMRI normalized intensity may allow identifying potentially useful response biomarkers correlating with survival, radiological response and biochemical progression.

Toxicity and Efficacy of Concurrent Androgen Deprivation Therapy, Pelvic Radiotherapy, and Radium-223 in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: Radium-223 is an alpha-emitting radionuclide associated with overall survival (OS) improvement in metastatic castration-resistant prostate cancer (mCRPC). External beam radiotherapy (EBRT) to prostate extends OS in men with metastatic hormone-sensitive prostate cancer (mHSPC) limited to less than 4 metastases. We hypothesized that combination radium-223 + pelvic EBRT could safely deliver maximal radiotherapy doses to primary and metastatic prostate cancer and may improve disease control. PATIENTS AND METHODS: Thirty patients with de novo bone metastatic mHSPC who had commenced androgen deprivation therapy (ADT) and docetaxel were recruited to this single-arm, open-label, prospective clinical trial: Neo-adjuvant Androgen Deprivation Therapy, Pelvic Radiotherapy and RADium-223 (ADRRAD; for new presentation T1-4 N0-1 M1B adenocarcinoma of prostate). Study treatments were: ADT, 6 cycles of radium-223 q28 days, conventionally fractionated prostate radiotherapy (74 Gy) and simultaneous integrated boost to pelvic lymph nodes (60 Gy). RESULTS: No grade 4/5 toxicity was observed. Three patients experienced grade 3 leukopenia, and 1 each experienced grade 3 neutropenia and thrombocytopenia; all were asymptomatic. One patient each experienced grade 3 dysuria and grade 3 urinary infection. No grade 3 gastrointestinal (GI) toxicity was observed. On treatment completion, there was a signal of efficacy; 24 (80%) patients had whole-body MRI evidence of tumor response or stability. Twenty-seven (90%) patients showed a reduction in alkaline phosphatase (ALP) compared with pretreatment levels. Median progression-free survival was 20.5 months. CONCLUSIONS: This is the first trial of combination ADT, radium-223, and EBRT to pelvis, post docetaxel. The combination was safe, with an efficacy signal. Multicenter randomized controlled trials (RCT) are warranted.

Development and Evaluation of a New Formative Assessment of Surgical Performance.

BACKGROUND: Formative assessment of operative performance is a mandatory part of surgical training. Engagement with assessment is limited in part by the time-consuming nature and the high perceived stakes of current assessment tools. OBJECTIVES: Our aims were to develop and collect validity evidence for a new operative assessment tool that addresses barriers to assessment that current trainers and trainees experience. METHODS: We developed the Generic Operative Supervised Learning Event (GOSLE). Orthopedic trainees were invited to complete GOSLEs with their trainers after surgical procedures. Experienced consultants assessed videotaped operations performed by trainees using the GOSLE. Validity evidence for content, relationships to other scores, internal structure, response process, and consequences of testing were evaluated. RESULTS: A total of 250 GOSLEs were completed. A strong correlation was found between the GOSLE scores and the Procedure-Based Assessment ratings (r = 0.87, p < 0.001). Rasch analysis confirmed satisfactory internal structure of the rating scale, with sequential increases in rating as performance improved. The reproducibility coefficient was 0.88, with 10 assessments of the same trainee who has to achieve a reliability coefficient of 0.8. Over 90% of users found the GOSLE easy to use, with most preferring it to other assessment methods. Feedback quality was higher using the GOSLE than with current assessments. CONCLUSION: We have collected validity evidence across multiple domains in support of the GOSLE. Its psychometric performance is comparable to that of current assessments. It is preferred by trainers and trainees over existing assessments. It stimulates high-quality, actionable feedback which better supports formative assessment. By addressing issues experienced with existing assessments, we expect engagement among users to be high.

Racial and Gender Influences on Pass Rates for the UK and Ireland Specialty Board Examinations.

INTRODUCTION: We explored effects of gender, ethnic origin, first language, and training status on scores in the Intercollegiate Specialty Board examinations in the UK and Ireland across the computer-marked written section and in the face-to-face oral and clinical section. METHODS: Demographic characteristics and examination results from 9987 attempts across 177 sittings from 2009 to 2013 were analyzed in an analysis of variance by training status, gender, ethnic origin, first language, and section (computer-marked multiple-choice examination vs face-to-face oral and clinical examination). RESULTS: We found increasing alignment between examiner and candidate characteristics during this period, with a 50% increase in examiners of Asian ethnic origin and a 60% increase in examiners whose first language is not English. The strongest factor in the analysis of variance was training status (F[2, 9818] = 27.67, p < 0.001), with candidates in training significantly outperforming others. Within "core candidates" (first attempt, in training), we found significant main effects for ethnic origin (F[5, 4809] = 2.36, p = 0.04), and first language (F[2, 4809] = 5.29, p = 0.003), but no interaction effects between these factors and section (both F < 1, p > 0.05). CONCLUSIONS: Training status was the most important factor in candidates' results. Although the analysis showed significant effects of ethnic origin and first language within "core candidates," these differences were statistically indistinguishable between the 2 sections of the examination, suggesting that the differential attainment by these factors cannot be attributed to examiner bias in a face-to-face examination.

Epidemiology of hospitalised osteochondritis dissecans in young people: incidence, geographical variation and trends over time in England from 2002 to 2010.

BACKGROUND: Osteochondritis dissecans (OCD) is an important cause of knee pain in physically active adolescents, but its aetiology remains controversial. Modern data on its epidemiology are lacking. The aim of this study was to analyse the hospitalised incidence, age and sex distribution, trends over time and geographical variation in OCD in the whole of England. METHODS: Hospital episode statistics (HES) data were analysed for OCD over the period 2002/3 to 2010/11 for England. HES datasets were record-linked so that anyone with multiple admissions for OCD was counted once only. RESULTS: The annual incidence rate for hospitalised OCD was 1.58 (95% CI 1.51-1.64) cases per 100,000 population. The peak age at diagnosis was 15-19 years for both sexes, and boys were affected more commonly than girls in the ratio 2:1. The hospitalised incidence of OCD varied significantly across England by government office region, from 1.05 (0.91-1.20) in London to 1.89 (1.70-2.09) in the North West Region. CONCLUSIONS: These data on the epidemiological features and trends over time in OCD provide new information about its basic epidemiological distribution. Its annual hospitalised incidence is about 1.6 cases per 100,000 population under 25 years, but varies significantly across England. These results have implications for planning rheumatology and orthopaedic services for both children and adults.

Arterial injury in total knee arthroplasty.

Arterial complications associated with knee arthroplasty are relatively rare, although probably underreported, complications of knee arthroplasty that carry a risk of significant morbidity. Thorough preoperative assessment and close liaison with a vascular surgeon, combined with an appreciation of common anatomical variants or distorted anatomy, may help prevent both thromboembolic and direct injuries from occurring. Clinical features of arterial complications following knee arthroplasty may vary significantly from acute hemorrhage or ischemia in the immediate postoperative period to chronic pain and swelling presenting even months following the procedure. There is potential for diagnostic confusion and delay that may adversely affect outcome. Early diagnosis along with vascular surgical review and intervention is key to successful management.