Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH).

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [18F]fluoromethyl-[1,2-2H4]choline ([18F]D4-FCH). [18F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1H/2D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [18F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [18F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [18F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12-16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival.

Hemolyzed Laboratory Specimens in the Emergency Department: An Underappreciated, but Frequent Problem.

INTRODUCTION: Hemolysis of blood samples from emergency department (ED) patients leads to delays in treatment and disposition. The aim of this study is to determine the frequency of hemolysis and variables predictive of hemolysis. METHODS: This observational cohort study was conducted among three institutions: academic tertiary care center and two suburban community EDs, with an annual census of over 270,000 ED visits. Data were obtained from the electronic health record. Adults requiring laboratory analysis with at least one peripheral intravenous catheter (PIVC) inserted within the ED were eligible. Primary outcome was hemolysis of lab samples and secondary outcomes included variables related to PIVC failure. RESULTS: Between January 8, 2021 and May 9, 2022, 141,609 patient encounters met inclusion criteria. The average age was 55.5 and 57.5% of patients were female. Hemolysis occurred in 24,359 (17.2%) samples. In a multivariate analysis, when compared to 20-gauge catheters, smaller 22-gauge catheters had an increased odds of hemolysis (OR 1.78, 95% confidence interval (CI) 1.65-1.91; P < .001), while larger 18-gauge catheters had a lower odds of hemolysis (OR 0.94; 95% CI 0.90-0.98; P = .0046). Additionally, when compared to antecubital placement, hand/wrist placement demonstrated increased odds of hemolysis (OR 2.06; 95% CI 1.97-2.15; P < .001). Finally, hemolysis was associated with a higher rate of PIVC failure (OR 1.06; 95%CI 1.00-1.13; P = 0.043). DISCUSSION: This large observational analysis demonstrates that lab hemolysis of is a frequent occurrence among ED patients. Given the added risk of hemolysis with certain placement variables, clinicians should consider catheter gauge/placement location to avoid hemolysis that may result in patient care delays and prolonged hospital stays.

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.

BACKGROUND: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). METHODS AND FINDINGS: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. CONCLUSIONS: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis.

BACKGROUND: We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit. METHODS: Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming-A'Hern exact phase II trial. Treatment comprised 4 cycles of vinflunine 320 mg/m2, given every 21 days. Primary endpoint was clinical benefit rate (CBR: objective responses plus stable disease) assessed after 4 cycles. Seven or more objective responses or disease stabilisations observed in 22 evaluable participants would exclude a CBR of <15%, with a true CBR of >40% being probable. RESULTS: Twenty-two participants were evaluable. Ten objective responses or disease stabilisations were confirmed. CBR was 45.5%, meeting the primary endpoint; partial response rate was 27.3%. Seven patients received >4 cycles of vinflunine. Dose reduction or treatment delay was required for 20% of cycles. In all, 68% of patients experienced at least one grade 3 adverse event. Two deaths on treatment were not caused by disease progression. CONCLUSIONS: Pre-specified clinical activity threshold was exceeded. Toxicity was in keeping with experience in other tumours. Vinflunine merits further study in this disease. TRIAL REGISTRATION: NCT02057913.

The impact of hegemonic masculine ideals on self-esteem in prostate cancer patients undergoing androgen deprivation therapy (ADT) compared to ADT-naïve patients.

PURPOSE: Androgen deprivation therapy (ADT) for Prostate Cancer (PCa) is associated with side effects that could lead to negative body image and low masculine self-esteem of survivors. We compared a group of PCa survivors following ADT with ADT-naïve patients, expecting the ADT group to show lower masculine self-esteem. We also expected patients with hegemonic masculinity ideals to show poorer masculine self-esteem and we hypothesized that ADT would moderate this relationship, expecting PCa patients on ADT with stronger hegemonic ideals to show the worst masculine self-esteem scores among study participants. METHODS: We compared 57 PCa survivors on ADT (Mage  = 64.16 (7.11)) to 59 ADT-naïve patients (Mage  = 65.25 (5.50)), on the Masculine Self-Esteem Scale (MSES), Body Image Scale (BIS), and Hegemonic Masculinity Ideals Scale (HMIS). RESULTS: While the two groups did not significantly differ on masculine self-esteem (F [1, 115] = 3.46, p = 0.065, ηp 2  = 0.029) and body image (F [1, 115] = 3.46, p = 0.065, ηp 2  = 0.029), younger age was significantly associated with higher body image issues (F [1, 115] = 8.63, p < 0.01, ηp 2  = 0.071, ß = -0.30). Hegemonic masculinity significantly predicted more masculine self-esteem related issues (t (2, 114) = 2.31, ß = 0.375, p < 0.05). ADT did not moderate this relationship. CONCLUSIONS: The results suggest that endorsing hegemonic masculinity could represent a risk factor for low masculine self-esteem regardless of ADT status and that younger age is associated with negative body image among PCa survivors. IMPLICATIONS: These results suggest the importance of inclusion of topics related to hegemonic masculinity when providing support to PCa survivors, both when discussing treatment side effects, as well as in the later phases of survivorship. This pilot also suggests that younger PCa survivors might benefit from body-image focused support regardless of treatment plan.

ROLE OF ANDROGEN RECEPTOR-TARGETED AGENTS IN LOCALIZED PROSTATE CANCER.

Anti-androgen therapy continues to be a basic pilar of treatment for both localized and metastatic prostate cancer. The advent of new generation of androgen receptor targeted agents (ARTA) transformed the care of patients with advanced disease. After such a success, the steps were taken to incorporate a new generation of ARTAs into the treatment landscape of localized prostate cancer. High-risk prostate cancer represents the most aggressive form of localized disease with significant metastatic potential and poor outcome. Here, the impact of novel therapies will likely be profound and transforming. This clinical space has already been a showcase for multidisciplinary treatment where the combination of local therapies with systemic treatment gradually improved patient outcomes and the chances of cure. The most recent step in redefining the treatment of localized disease is the adoption of novel ARTAs moving forward the multidisciplinary platform. In this narrative review, we discuss current clinical evidence supporting the use of novel ARTAs in patients with localized high-risk prostate cancer and cover recent developments in biomarker-driven strategies for treatment individualization in this clinical context.

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial.

BACKGROUND: The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. METHODS: We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). INTERPRETATION: These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. FUNDING: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.

Rectal spacers in patients with prostate cancer undergoing radiotherapy: A survey of UK uro-oncologists.

AIM: To understand the awareness and use of rectal spacers for prostate cancer patients undergoing radical radiotherapy in the United Kingdom. METHODS: An expert-devised online questionnaire was completed by members of the British Uro-oncology Group (BUG). RESULTS: Sixty-three specialists completed the survey (50% of BUG members at that point in time). Only 37% had used rectal spacers, mostly for private patients or those with pre-existing bowel conditions. However, many (68%) would like to use these devices in future. More than 70% of the uro-oncologists felt that bowel toxicity was underreported, but 60% believed that the use of radiotherapy without bowel toxicity was achievable with the use of rectal spacers. CONCLUSIONS: The current use of rectal spacers by UK uro-oncologists for patients with localised or locally advanced prostate cancer receiving radiotherapy is low and largely restricted by resourcing issues.

Management of newly diagnosed metastatic hormone-sensitive prostate cancer: A survey of UK Uro-oncologists.

AIM: To explore the practice and views of uro-oncologists in the United Kingdom regarding their use of chemotherapy and androgen receptor-targeted agents (ARTAs) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: An expert-devised paper or online questionnaire was completed by members of the British Uro-oncology Group. RESULTS: All respondents stated that they would offer patients with newly diagnosed mHSPC docetaxel and androgen deprivation therapy (ADT) if they were sufficiently fit to receive chemotherapy (this was the only option available at the time of the survey); 64% would strongly recommend docetaxel for those with high-volume metastatic disease and 31% for those with low-volume disease. Hypothetically, if both docetaxel and ARTAs were available in the United Kingdom for mHSPC, almost 65% of respondents would recommend an ARTA with ADT to these patients in at least one-half of all cases, with the strongest recommendations to patients with high-risk disease. Imaging for the response was conducted according to suspicion of disease progression, regardless of treatment, with the minority of clinicians recommending routine imaging. If a choice of therapy was available, docetaxel would be more likely to be offered to patients with liver or lung metastases, and ARTAs to patients with bone or lymph node only metastases. Almost all respondents would offer local radiotherapy to the primary tumour in patients with low-volume disease. CONCLUSION: All the UK uro-oncologists surveyed stated that they would offer docetaxel in combination with ADT to all newly diagnosed patients with mHSPC if fit enough for chemotherapy. ARTAs would be offered to many patients if available, especially those with high-risk disease or those unfit to receive chemotherapy. Scanning was typically conducted following treatment only at the suspicion of disease progression.

Left Ventricular Ejection Fraction Assessment by Emergency Physician-Performed Bedside Echocardiography: A Prospective Comparative Evaluation of Multiple Modalities.

BACKGROUND: Although there is some support for visual estimation (VE) as an accurate method to estimate left ventricular ejection fraction (LVEF), it is also scrutinized for its subjectivity. Therefore, more objective assessments, such as fractional shortening (FS) or e-point septal separation (EPSS), may be useful in estimating LVEF among patients in the emergency department (ED). OBJECTIVE: Our aim was to compare the real-world accuracy of VE, FS, and EPSS using a sample of point-of-care cardiac ultrasound transthoracic echocardiography (POC-TTE) images acquired by emergency physicians (EPs) with the gold standard of Simpson's method of discs, as measured by comprehensive cardiology-performed echocardiography. METHODS: We conducted a single-site prospective observational study comparing VE, FS, and EPSS to assess LVEF. Adult patients in the ED receiving both POC-TTE and comprehensive cardiology TTE were included. EPs acquired POC-TTE images and videos that were then interpreted by 2 blinded EPs who were fellowship-trained in emergency ultrasound. EPs estimated LVEF using VE, FS, and EPSS. The primary outcome was accuracy. RESULTS: Between April and May 2018, 125 patients were enrolled and 113 were included in the final analysis. EP1 and EP2 had a κ of 0.94 (95% confidence interval [CI] 0.87-1.00) and 0.97 (95% CI 0.91-1.00), respectively, for VE compared with gold standard, a κ of 0.40 (95% CI 0.23-0.57) and 0.38 (95% CI 0.18-0.57), respectively, for EPSS compared with gold standard, and a κ of 0.70 (95% CI 0.54-0.85) and 0.66 (95% CI 0.50-0.81), respectively, for FS compared with gold standard. Sensitivity of severe dysfunction was moderate to high in VE (EP1 85% and EP2 93%), poor to moderate in FS (EP1 73% and EP2 50%), and poor in EPSS (EP1 11% and EP2 18%). CONCLUSIONS: Using a real-world sample of POC-TTE images, the quantitative measurements of EPSS and FS demonstrated poor accuracy in estimating LVEF, even among experienced sonographers. These methods should not be used to determine cardiac function in the ED. VE by experienced physicians demonstrated reliable accuracy for estimating LVEF compared with the gold standard of cardiology-performed TTE.

Ultralong Versus Standard Long Peripheral Intravenous Catheters: A Randomized Controlled Trial of Ultrasonographically Guided Catheter Survival.

STUDY OBJECTIVE: Ultrasonographically guided intravenous peripheral catheters have dismal dwell time, with most intravenous lines failing before completion of therapy. Catheter length in the vein is directly related to catheter longevity. We investigate the survival of an ultralong ultrasonographically guided intravenous peripheral catheter compared with a standard long one. METHODS: We conducted a single-site, nonblinded, randomized trial of catheter survival. Adult patients presenting to the emergency department with difficult vascular access were recruited and randomized to receive either standard long, 4.78-cm, 20-gauge ultrasonographically guided intravenous peripheral catheters or ultralong, 6.35-cm, 20-gauge ultrasonographically guided intravenous peripheral catheters. The primary outcome was duration of catheter survival. The secondary outcome was the optimal length of the catheter in the vein to maximize survival. Additional intravenous-related endpoints included first-stick success, time to insertion, number of attempts, thrombosis, and infection. RESULTS: Between October 2018 and March 2019, 257 patients were randomized, with 126 in the standard long ultrasonographically guided intravenous peripheral catheter group and 131 in the ultralong group. Kaplan-Meier estimate of catheter median survival time in the ultralong group was 136 hours (95% confidence interval [CI] 116 to 311 hours) compared with 92 hours (95% CI 71 to 120 hours) in the standard long group, for a difference of 44 hours (95% CI 2 to 218 hours). The optimal catheter length in the vein was 2.75 cm, and intravenous lines with greater than 2.75 cm inserted had a median survival of 129 hours (95% CI 102 to 202 hours) compared with 75 hours (95% CI 52 to 116 hours) for intravenous lines with less than or equal to 2.75 cm, for a difference of 54 hours (95% CI 10 to 134 hours). Insertion characteristics were similar between the groups: 74.1% versus 79.4% first-stick success (95% CI for the difference -2% to 5%), 1.4 versus 1.3 for number of attempts (95% CI for the difference -0.1 to 0.3), and 6.9 versus 5.9 minutes to completion (95% CI for the difference -1.3 to 3.4) with ultralong versus standard long, respectively. There were no cases of infection or thrombosis. CONCLUSION: This study demonstrated increased catheter survival when the ultralong compared with the standard long ultrasonographically guided intravenous peripheral catheter was used, whereas insertion characteristics and safety appeared similar.

Can radiation-induced lower urinary tract disease be ameliorated in patients treated for pelvic organ cancer: ICI-RS 2019?

AIMS: This article reviews the clinical outcomes and basic science related to negative effects of radiotherapy (RT) on the lower urinary tract (LUT) when used to treat pelvic malignancies. METHODS: The topic was discussed at the 2019 meeting of the International Consultation on Incontinence-Research Society during a "think tank" session and is summarized in the present article. RESULTS: RT is associated with adverse effects on the LUT, which may occur during treatment or which can develop over decades posttreatment. Here, we summarize the incidence and extent of clinical symptoms associated with several modes of delivery of RT. RT impact on normal tissues including urethra, bladder, and ureters is discussed, and the underlying biology is examined. We discuss innovative in vivo methodologies to mimic RT in the laboratory and their potential use in the elucidation of mechanisms underlying radiation-associated pathophysiology. Finally, emerging questions that need to be addressed through further research are proposed. CONCLUSIONS: We conclude that RT-induced negative effects on the LUT represent a significant clinical problem. Although this has been reduced with improved methods of delivery to spare normal tissue, we need to (a) discover better approaches to protect normal tissue and (b) develop effective treatments to reverse radiation damage.

Use of bisphosphonates and other bone supportive agents in the management of prostate cancer-A UK perspective.

AIM: To explore the practice and views of uro-oncologists in the UK regarding their use of bone supportive agents in patients with prostate cancer. METHODS: An expert-devised online questionnaire was completed by members of the British Uro-oncology Group (BUG). RESULTS: Of 160 uro-oncologists invited, 81 completed the questionnaire. Approximately 70% of respondents never use a bone supportive agent in patients with metastatic hormone-naïve prostate cancer on androgen deprivation therapy (ADT). However, use was more frequent in men with metastatic castration-resistant prostate cancer, from first-line treatment onwards. The majority of uro-oncologists do not use a bone supportive agent to prevent skeletal-related events in men with non-metastatic disease unless the individual patient is at an increased risk of osteoporosis. In men with more advanced disease, respondents would use an oral or intravenous (IV) bisphosphonate in 41% and 61% of patients, respectively. Zoledronic acid is the first-choice bone supportive treatment in 77% of cases, with the lack of clinical data cited as a barrier to use for other IV bisphosphonates. Local guidelines also have a significant influence on the use of bone supportive agents, especially with respect to denosumab. Bone mineral density measurement is conducted in approximately 40% of men with ADT exposure of 2 years or longer, or those with metastatic prostate cancer. CONCLUSION: Uro-oncologists in the UK generally do not use bone supportive agents for men with metastatic hormone-naïve prostate cancer or those with non-metastatic disease. However, increasing the duration of ADT and the presence of castration-resistant metastatic prostate cancer increases use.

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.

BACKGROUND: Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy. METHODS: We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number NCT00268476. FINDINGS: Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63-73) and median amount of prostate-specific antigen of 97 ng/mL (33-315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68-0·84; p<0·0001) but not overall survival (0·92, 0·80-1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3-4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy). INTERPRETATION: Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.

Analysis of volumetric and dosimetric changes in mid treatment CT scan in carcinoma nasopharynx: implications for adaptive radiotherapy.

OBJECTIVE: Carcinoma of nasopharynx is a radiosensitive tumor and therapeutic response during radiation treatment can result in dosimetric variations in the delivered dose to the tumor and critical organs. This study was done to evaluate the volumetric and dosimetric changes seen in tumor tissue and organs at risk in a mid treatment planning scan and its implications for adaptive replanning. Twenty patients of locally advanced carcinoma nasopharynx were evaluated. All patients were started on treatment with a baseline treatment plan on SIB-VMAT. To evaluate volumetric and dosimetric changes during treatment, a mid treatment CT scan (MTS) was taken at the 17th fraction of treatment and compared with the baseline planning CT scan (BS). Adaptive treatment plans were generated on the MTS and further treatment was continued on the adaptive plans. The mean weight loss observed at the 17th fraction of treatment was 3.4 ± 2.6 kg(Mean±S.D). The mean neck diameter at C2 level was 14.19±1.02 and 13.29 ± 1.14 cm in the BS and MTS respectively (p=0.001). The GTV 70 volume showed a 29.16% volume loss. The mean doses received by the right and left parotids were 25.45±0.98 and 24.64±3.8 Gy in the baseline treatment plan and 33.21±11.29 (p=0.054) and 31.76±8.44 Gy respectively in the MTS (p=0.016) The mean weight loss showed a statistically significant correlation with increase in the right parotid(p=0.043) and left parotid doses(p=0.024). Weight loss during treatment combined with volume changes in target tissues mandate routine adaptive replanning while treating carcinoma nasopharynx.

Body image issues and attitudes towards exercise amongst men undergoing androgen deprivation therapy (ADT) following diagnosis of prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) is an established treatment for prostate cancer (PCa), but its side-effects can affect body appearance and functioning. However, research into the impact of ADT on body image is limited. Exercise can help patients to counterbalance some side-effects, potentially improving body image too. However, adherence to exercise recommendations is low. Therefore, we explored body image after ADT and attitudes towards exercise. METHODS: Twenty two semi-structured interviews were conducted with PCa patients receiving ADT (Mage = 67.9 years old, SD = 9.99). RESULTS: Participants expressed appearance dissatisfaction focusing on body feminization. Participants exercised to counterbalance ADT side-effects and improve mood. Exercise also helped them to re-establish a sense of control over their body and experience a sense of achievement. However, some men described being worried that their appearance and physical performance would be judged by others, so they often exercised alone or gave up exercise. Time management and fatigue were also identified as exercise barriers. CONCLUSION: These findings highlight the need to further investigate body image concerns and exercise barriers in PCa patients undergoing ADT. These results could also inform support groups and health care professionals on the topic. However, further research should explore the most effective and acceptable ways to provide support to PCa patients on body image issues.

Standard long IV catheters versus extended dwell catheters: A randomized comparison of ultrasound-guided catheter survival.

INTRODUCTION: Establishing peripheral intravenous (IV) access is a vital step in providing emergency care. Ten to 30% of Emergency Department (ED) patients have difficult vascular access (DVA). Even after cannulation, early failure of US-guided IV catheters is a common complication. The primary goal of this study was to compare survival of a standard long IV catheter to a longer extended dwell catheter. METHODS: This study was a prospective, randomized comparative evaluation of catheter longevity. Two catheters were used in the comparison: [1] a standard long IV catheter, the 4.78 cm 20 gauge Becton Dickinson (BD); and [2] a 6 cm 3 French (19.5 gauge) Access Scientific POWERWAND™ extended dwell catheter (EDC). Adult DVA patients in the ED with vein depths of 1.20 cm-1.60 cm and expected hospital admissions of at least 24 h were recruited. RESULTS: 120 patients were enrolled. Ultimately, 70 patients were included in the survival analysis, with 33 patients in the EDC group and 37 patients in the standard long IV group. EDC catheters had lower rates of failure (p = 0.0016). Time to median catheter survival was 4.04 days for EDC catheters versus 1.25 days for the standard long IV catheter. Multivariate survival analysis also showed a significant survival benefit for the EDC catheter (p = 0.0360). CONCLUSION: A longer extended dwell catheter represents a viable and favorable alternative to the standard longer IVs used for US-guided cannulation of veins >1.20 cm in depth. These catheters have significantly improved survival rates with similar insertion success characteristics.

Measuring testosterone and testosterone replacement therapy in men receiving androgen deprivation therapy for prostate cancer: A survey of UK uro-oncologists' opinions and practice.

AIM: To explore the practice and attitudes of uro-oncologists in the UK regarding monitoring testosterone levels and the use of testosterone replacement therapy (TRT) in their prostate cancer patients treated with androgen deprivation therapy (ADT). METHODS: An expert-devised online questionnaire was completed by the members of the British Uro-oncology Group (BUG). RESULTS: Of 160 uro-oncologists invited, 84 completed the questionnaire. Before initiating ADT in patients with non-metastatic prostate cancer, only 45% of respondents measured testosterone levels and 61% did not measure testosterone at all during ADT in the adjuvant or neoadjuvant setting. However, in men with metastatic prostate cancer, 71% of the uro-oncologists measured testosterone before starting ADT and the majority continued testing during treatment. Approximately two-thirds of respondents did not prescribe TRT for their patients who were in remission following neo(adjuvant) ADT and who had castration levels of testosterone. DISCUSSION: Among UK uro-oncologists, the measurement of testosterone levels before and during ADT was not typically part of routine practice in the management of patients with prostate cancer. However, testosterone levels were checked more frequently for patients with metastatic disease than disease at an earlier stage. Testing could be conducted in parallel with PSA measurement as testosterone levels are linked to biochemical failure. The majority of specialists participating in the survey did not prescribe TRT for their patients in remission following ADT. CONCLUSION: Uro-oncologists in the UK do not generally measure testosterone as part of their patient management and they remain cautious about the possible benefits of TRT in men with prostate cancer.

Healthcare resource utilisation associated with skeletal-related events in European patients with multiple myeloma: Results from a prospective, multinational, observational study.

OBJECTIVES: Patients with multiple myeloma (MM) often experience debilitating skeletal-related events (SREs: pathologic fracture, radiation to bone [RB], surgery to bone [SB] or spinal cord compression [SCC]). This is the first comprehensive, prospective, observational analysis of healthcare resource utilisation (HRU), independently attributed to SREs by investigators, in patients with MM. METHODS: Eligible patients had lytic bone lesions, life expectancy ≥6 months, Eastern Cooperative Oncology Group performance status ≤2 and ≥1 SRE in the 97 days before enrolment. Data were collected retrospectively for 97 days before enrolment and prospectively for 18-21 months. RESULTS: Altogether, 153 patients were enrolled from Germany, Italy, Spain and the United Kingdom. Of the 281 observed SREs, 36.7% required inpatient stays (mean duration: 20.6 days per SRE [standard deviation (SD): 22.9]). SB and SCC were the SREs most likely to require stays (72.3% and 50.0% of SREs, respectively); SCC required the longest mean (SD) stay per event (40.5 [40.8] days). Overall, 179 SREs required outpatient visits; this was most likely for RB (74.8%) and least likely for non-vertebral fracture (50.0%). CONCLUSIONS: All SREs were associated with substantial HRU; therefore, preventing SREs in MM will reduce the economic and resource burden on healthcare systems.

Physicians' preferences for bone metastases treatments in France, Germany and the United Kingdom.

BACKGROUND: Several bone-targeted agents (BTAs) are available for preventing skeletal-related events (SREs), but they vary in terms of efficacy, safety and mode of administration. This study assessed data on European physicians' treatment preferences for preventing SREs in patients with bone metastases from solid tumours. METHODS: Physicians completed a web-based discrete-choice experiment survey of 10 choices between pairs of profiles of hypothetical BTAs for a putative patient. Each profile included five attributes within a pre-defined range (primarily based on existing BTAs' prescribing information): time (months) until the first SRE; time (months) until worsening of pain; annual risk of osteonecrosis of the jaw (ONJ); annual risk of renal impairment; and mode of administration. Choice questions were developed using an experimental design with known statistical properties. A separate main-effects random parameters logit model was estimated for each country and provided the relative preference for the treatment attributes in the study. RESULTS: A total of 191 physicians in France, 192 physicians in Germany, and 197 physicians in the United Kingdom completed the survey. In France and the United Kingdom, time until the first SRE and risk of renal impairment were the most important attributes; in Germany, time until the first SRE and delay in worsening of pain were the most important. In all countries, a 120-min infusion every 4 weeks was the least preferred mode of administration (p < 0.05) and the annual risk of ONJ was judged to be the least important attribute. CONCLUSIONS: When making treatment decisions regarding the choice of BTA, delaying the onset of SREs/worsening of pain and reducing the risk of renal impairment are the primary objectives for physicians.