Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

Background: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. Patients and methods: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. Results: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < −2.5 standard deviation). Conclusions: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherap

First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07)

Background: Oral temozolomide has shown similar efficacy to dacarbazine in phase III trials with median progression-free survival (PFS) of 2.1 months. Bevacizumab has an inhibitory effect on the proliferation of melanoma and sprouting endothelial cells. We evaluated the addition of bevacizumab to temozolomide to improve efficacy in stage IV melanoma. Patients and methods: Previously untreated metastatic melanoma patients with Eastern Cooperative Oncology Group performance status of two or more were treated with temozolomide 150 mg/m2 days 1-7 orally and bevacizumab 10 mg/kg body weight i.v. day 1 every 2 weeks until disease progression or unacceptable toxicity. The primary end point was disease stabilisation rate [complete response (CR), partial response (PR) or stable disease (SD)] at week 12 (DSR12); secondary end points were best overall response, PFS, overall survival (OS) and adverse events. Results: Sixty-two patients (median age 59 years) enrolled at nine Swiss centres. DSR12 was 52% (PR: 10 patients and SD: 22 patients). Confirmed overall response rate was 16.1% (CR: 1 patient and PR: 9 patients). Median PFS and OS were 4.2 and 9.6 months. OS (12.0 versus 9.2 months; P = 0.014) was higher in BRAF V600E wild-type patients. Conclusions: The primary end point was surpassed showing promising activity of this bevacizumab/temozolomide combination with a favourable toxicity profile. Response and OS were significantly higher in BRAF wild-type patient

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Lower lid entropion secondary to treatment with alpha-1a receptor antagonist: a case report

<p>Abstract</p> <p>Introduction</p> <p>The use of alpha-1a receptor antagonists (tamsulosin) is widely accepted in the treatment of benign prostatic hypertrophy (BPH). It has previously been implicated as a causative agent in intra-operative floppy iris syndrome due to its effects on the smooth muscle. We report a case of lower lid entropion that may be related to a patient commencing treatment of tamsulosin.</p> <p>Case presentation</p> <p>A 74-year-old Caucasian man was started on alpha 1-a receptor antagonist (Tamsulosin) treatment for benign prostatic hypertrophy. Eight days later, he presented to the ophthalmology unit with a right lower lid entropion which was successfully treated surgically with a Weiss procedure.</p> <p>Conclusion</p> <p>We report a case of lower lid entropion that may be secondary to the recent use of an alpha-1a blocker (tamsulosin). This can be explained by considering the effect of autonomic blockade on alpha-1 receptors in the Muller's muscle on a patient that may already have an anatomical predisposition to entropion formation due to a further reduction in muscle tone.</p

Paediatric magnetic resonance imaging adaptations without the use of sedation or anaesthesia: A narrative review

Magnetic Resonance Imaging (MRI) produces images with high soft tissue contrast without the use of ionising radiation, making it a valuable tool for scanning paediatrics. However, it can be difficult to scan children when they are awake, resulting often in poor image quality scans and necessitating the use of sedation and general anaesthesia (GA). The aim of sedation and anaesthesia is to reduce anxiety and movement during image acquisition, thereby improving compliance and image quality. However, there are adverse risks and costs to their use, leading to the need to consider alternative imaging adaptation methods. This research discussed potential methods of reducing anxiety and improving paediatric compliance during MRI examinations, by assessing their feasibility for use in the clinical setting. The literature suggests that adaption strategies and modification of radiographer techniques were mostly effective in reducing the requirement of sedation/GA

Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors

INTRODUCTION: Treatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors. BACKGROUND: METHODS: Patients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simon’s Optimal 2-stage design was used to determine efficacy. Primary endpoints included objective response (OR) and long-term stable disease (LTSD) rates. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 46 patients were evaluable for response (HGG, n = 19; DIPG, ependymoma, and medulloblastoma, n = 9 each). Two patients with HGG achieved OR or LTSD (10.5% [95% CI, 1.3%-33.1%]; 1 partial response and 1 LTSD) and 1 patient with ependymoma had LTSD (11.1% [95% CI, 0.3%-48.2%]). There were no ORs or LTSD in the DIPG or medulloblastoma cohorts. The median PFS for patients with HGG, DIPG, ependymoma, and medulloblastoma was 7.86, 11.29, 8.43, and 8.43 weeks, respectively. Median OS was 5.06, 3.78, 12.02, and 11.60 months, respectively. Neutropenia was the most common grade 3/4 adverse event. CONCLUSIONS: Treatment with POM monotherapy did not meet the primary measure of success in any cohort. Future studies are needed to evaluate if POM would show efficacy in tumors with specific molecular signatures or in combination with other anticancer agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25

Strategies to improve the magnetic resonance imaging experience for autistic individuals: a cross-sectional study exploring parents and carers’ experiences

Background: Autistic individuals encounter numerous barriers in accessing healthcare, including communication difficulties, sensory sensitivities, and a lack of appropriate adjustments. These issues are particularly acute during MRI scans, which involve confined spaces, loud noises, and the necessity to remain still. There remains no unified approach to preparing autistic individuals for MRI procedures. Methods: A cross-sectional online survey was conducted with parents and carers of autistic individuals in the UK to explore their experiences, barriers, and recommendations concerning MRI scans. The survey collected demographic information and experiential accounts of previous MRI procedures. Quantitative data were analysed descriptively, while key themes were identified within the qualitative data through inductive thematic analysis. Results: Sixteen parents/carers participated. The majority reported difficulties with communication, inadequate pre-scan preparation, and insufficient adjustments during MRI scans for their autistic children. Key barriers included an overwhelming sensory environment, radiographers’ limited understanding of autism, and anxiety stemming from uncertainties about the procedure. Recommended improvements encompassed accessible communication, pre-visit familiarisation, noise-reduction and sensory adaptations, staff training on autism, and greater flexibility to meet individual needs. Conclusions: There is an urgent need to enhance MRI experiences for autistic individuals. This can be achieved through improved staff knowledge, effective communication strategies, thorough pre-scan preparation, and tailored reasonable adjustments. Co-producing clear MRI guidelines with the autism community could standardise sensitive practices. An individualised approach is crucial for reducing anxiety and facilitating participation. Empowering radiographers through autism-specific education and incorporating insights from autistic individuals and their families could transform MRI experiences and outcomes