Hemi-ablative low-dose-rate prostate brachytherapy for unilateral localised prostate cancer.

OBJECTIVES: To report clinical outcomes of the Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluating treatment-related toxicity and effectiveness of hemi-gland (HG) low-dose-rate (LDR) prostate brachytherapy as a focal approach to control unilateral localised prostate cancer. PATIENTS AND METHODS: Single institution phase IIS pilot study of patients treated with focal 4D Brachytherapy™ (BXTAccelyon, Burnham, Buckinghamshire, UK). The primary outcome was patient-reported toxicity 24 months after implant. The secondary outcome was assessment of disease control. Outcomes in HG patients were compared to whole-gland (WG) controls obtained from our prospective cohort registry by negative binomial and linear regression models. RESULTS: Pre-treatment demography was similar between the 30 HG patients and 362 WG controls. Post-implant dosimetry was similar for the prostate gland target volumes and significantly reduced for the urethra and bowel in HG patients relative to WG controls, but this did not translate into a difference in post-implant mean symptom scores between the two groups. Nevertheless, the change in score from baseline indicated that the impact on pre-treatment symptom status was less after HG implants. Only HG patients showed a return to baseline urinary scores as early as 12 months. Sexual potency was conserved in 73% and 67% of HG and WG patients, respectively (P = 0.84). Post-implant prostate-specific antigen (PSA) kinetics revealed that baseline PSA was reduced at 24 months by 78% and 88% in HG and WG patients, respectively (P < 0.05). Treatment relapse occurred in one (3%) HG patient 55 months after implant and in nine (3%) WG patients at 32-67 months after implant. CONCLUSION: This pilot study suggests that treatment-related toxicity and biochemical outcomes after HG implants are broadly similar to those observed with WG treatment despite the lower dose delivered by HG implants.

The Role of the Multiparametric MRI LiverMultiScanTM in the Quantitative Assessment of the Liver and Its Predicted Clinical Applications in Patients Undergoing Major Hepatic Resection for Colorectal Liver Metastasis.

Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.

Is hemi-gland focal LDR brachytherapy as effective as whole-gland treatment for unilateral prostate cancer?

PURPOSE: The Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluated hemi-gland (HG) low-dose-rate prostate brachytherapy (LDR-PB) as a focal approach to control unilateral localized prostate cancer and reduce treatment-related toxicity at 2-years postimplant. Herewith we present further outcomes with a minimum of 5 years post-implant follow-up. METHODS AND MATERIALS: Outcomes of 30 HG implants and 362 whole-gland (WG) brachytherapy controls were monitored with IPSS, urinary Quality-of-Life (QoLU), GI component of EORTC-PR25 (QoLB), and IIEF-5 instruments, and PSA values. The median (range) follow-up for HG and WG cases was 72 (60-96) months and 84 (24-144) months respectively. RESULTS: The IPSS was significantly reduced in HG relative to WG patients and trends indicating improved bowel QoL and erectile function were observed. The mean of change in PSA from baseline to last follow-up was -5.6 and -6.5 in HG and WG respectively (p = 0.1). The mean time to nadir was 4.2 and 4.8 years in HG and WG respectively (p = 0.06). Over time PSA in HG patients mirrored the sustained decline observed in WG cases but levels were higher by an average 0.5 ng/ml over WG controls (p < 0.001). Treatment failure occurred in 2 (6.7%) HG patients and in 20 (5.5%) WG cases. Five-year relapse-free survival was 97% in both groups (p = 0.7). CONCLUSIONS: At 5 years postimplant HG LDR-PB was as effective as WG treatment for control of unilateral localized prostate cancer with moderate improvement in treatment-related symptoms. Importantly, PSA is a valuable marker to assess disease control in this form of focal therapy.

MicroRNA 8059 as a marker for the presence and extent of coronary artery calcification.

Objective: MicroRNAs (miRNAs) may serve as potential biomarkers in a variety of pathologies. The aim of this study was to determine whether miRNAs could serve as blood-based markers of isolated coronary artery calcification (CAC) defined as CAC in the absence of an underlying metabolic abnormality. Methods: 24 age-matched and sex-matched patients who had been referred for elective CT coronary calcium score and angiography as part of investigation for cardiac chest pain were recruited. Peripheral venesection was performed and an Agatston calcium score was derived from the CT coronary angiogram using default software. RNA was extracted using the LeukoLOCK Total RNA Isolation System for Toray's microarray analysis and quantitative reverse transcription PCR (qRT-PCR). Results: The patients were well matched for age, sex and conventional risk factors for coronary artery disease. Microarray analysis identified lower expression of miRNA-138-2-3p, miRNA-1181, miRNA-6816-3p and miRNA-8059 in patients with coronary artery calcium score (CACS)=0 vs CACS>100. qRT-PCR confirmed significant downregulation of miRNA-8059 in patients with CACS>100 (CACS=0 vs CACS>100; P=0.03). Conclusion: miRNA-8059 may serve as a peripheral blood-based biomarker for the presence of CAC, as well as provide a platform for studying the pathophysiological basis of isolated CAC. Trial registration number: NCT01992848; Results.

The HASTE Protocol: a standardised CT Coronary Angiography service operated from a District General Hospital.

Introduction: CT coronary angiography (CTCA) has excellent sensitivity but lacks specificity when compared with invasive coronary angiography (ICA) particularly in patients with a high coronary calcium burden. CTCA has been shown in large trials to decrease the requirement for diagnostic ICA and provide diagnostic clarity. We describe the methodology used to provide a standardised CTCA service established in a District General Hospital, which may assist other hospitals aiming to develop a cardiac CT service. Methods: Scan request forms, authorisation and patient instruction were recorded. Patient preparation prior to CTCA as well as exclusion and inclusion criteria were documented. Scans were interpreted using a multidisciplinary team (MDT) approach in order to organise follow-up, medication and further investigation. Results: Over 6 months, 157 consecutive scans were performed. CTCA was completed in 88% (n=138/157) and considered of diagnostic quality in 82% (n=129/157). The median radiation dose was 3.42 mSv. Overall, 64% of patients had evidence of coronary calcium. Following MDT review, 72% (n=113/157) of patients were discharged without requiring invasive angiography. 15% (n=24/157) of patients went on to have invasive angiography showing non-obstructive disease and 13% (20/157) of patients underwent percutaneous coronary intervention (11%) or bypass surgery (1%). Discussion: Appropriate referrals, patient preparation and scan quality remain significant factors in running a CTCA service. Despite this, the vast majority of patients can be discharged on the basis of the CTCA alone. An MDT approach is key to the delivery of a cardiac CT service.

On the Irrelevance of Neuromyths to Teacher Effectiveness: Comparing Neuro-Literacy Levels Amongst Award-Winning and Non-award Winning Teachers.

A number of studies have recently demonstrated a high level of belief in 'neuromyths' (fallacious arguments about the brain) amongst trainee and non-award winning educators. The authors of these studies infer this to mean that acceptance of these neuromyths has a negative impact on teaching effectiveness. In this study, we explored this assumption by assessing the prevalence of neuromyth acceptance amongst a group of internationally recognized, award-winning teachers and comparing this to previously published data with trainee and non-award winning teacher populations. Results revealed the acceptance of neuromyths to be nearly identical between these two groups, with the only difference occurring on 2 (out of 15) items. These findings suggest that one cannot make simple, unqualified arguments concerning the relationship between belief in neuromyths and teacher effectiveness. In fact, the idea that neuromyths negatively impact upon teaching might, itself, be a neuromyth.

Hemi-gland focal low dose rate prostate brachytherapy: An analysis of dosimetric outcomes.

BACKGROUND AND PURPOSE: Advances in magnetic resonance imaging (MRI) and prostate sampling enable early identification of men with low to intermediate risk prostate cancer who are candidates for focal therapies that minimise side effects. We report dosimetry data from a pilot study evaluating the effectiveness of hemi-gland low dose rate (HG-LDR) brachytherapy as a focal therapy approach to control unilateral localised disease. MATERIAL AND METHODS: Twenty-two men underwent HG-LDR brachytherapy. Multi parametric MRI and transperineal template mapping biopsies were used to identify low volume unilateral disease. Whole gland therapy controls (n=120) were retrospectively obtained. All implants were performed with 4D Brachytherapy. RESULTS: Intraoperative and postimplant dosimetry complied with established brachytherapy parameters. Mean (standard deviation) postoperative D90 for the target hemi-gland was 153.8 (11.3) Gy compared to 47.5 (12.7) Gy for the contralateral hemi-gland (P<0.001). Mean postoperative V100% was 93.1 (3.9) and 24.6 (10.5) for the target and contralateral hemi-glands respectively (P<0.001). Urethra D30 was 150.4 (19.8) Gy and 174.2 (15.0) Gy for hemi-gland and whole gland implants respectively (P<0.001). Significantly reduced dose was also observed for rectum and neurovascular bundles. CONCLUSIONS: HG-LDR focal brachytherapy is feasible with significant reduction in dose to the contralateral hemi-gland and organs at risk.