Triple-negative breast cancer: Current perspective on the evolving therapeutic landscape

Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy

Precision of Age Estimation in Goldlined Seabream Rhabdosargus sarba (Sparidae) from the Arabian Sea, Oman

Accurate age determination of commercial fish is vital to successful fisheries management. Reliable age determination is essential for almost all aspects of fishery research, especially for study of growth, production, population structure and dynamics. The validation of aging methods is an important step in estimating growth and longevity. This study presents the validation of otolith-reading method for age estimation of goldlined seabream Rhabdosargus sarba. A total of 1185 goldlined seabream otoliths collected from the Arabian Sea of which 350 specimens were read by two different readers for whole and sectioned otoliths. Age comparisons between whole and thin-sectioned otoliths showed agreement in age readings for age groups 2-5 years and the whole otoliths tended to give lower ages than those estimated by thin sections. APE ranged from 3 to 7% for the three readings. Common differences between readers were related to interpretation of the otolith edge type and to interpretation of the first annulus. Keywords: Sparidae, Rhabdosargus sarba, Otolith; age; average percent error; management

Study on the Influence of Polymer/Particle Properties on the Resilience of Superhydrophobic Coatings.

Enhancement in the resilience of superhydrophobic coatings is crucial for their future applicability. However, the progress in this aspect is currently limited due to the lack of a consistent resilience analysis methodology/protocol as well as the limited understanding of the influence of the materials components on the resultant coating performance. This study applies a quantitative analysis methodology involving image analysis and mass tracking and utilizes it to investigate how the properties of coating components can influence coating resilience. The factors examined were changing the molecular weight/tensile strength of poly(vinylchloride)/poly(dimethylsiloxane) (PVC/PDMS) polymers and changing the size of the roughening particles. In addition to the examination of resilience data to evaluate degradation patterns, three-dimensional (3D) mapping of the scratches was performed to obtain an insight into how material removal occurs during abrasion. The results can indicate preferential polymer selection (using higher-molecular-weight polymers for PVC) and optimal particle sizes (smaller particles) for maximizing coating resilience. The study, although focused on superhydrophobic materials, demonstrates wide applicability to a range of areas, particularly those focused on the development of high-strength coatings

Prolonged treatment with vitamin D in postmenopausal women with primary hyperparathyroidism

Introduction/background: Vitamin D deficiency further increases circulating parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism (pHPT), with potential detrimental effects on bone mass. Methods: This was an observational clinical study in consecutive conservatively treated postmenopausal women (n=40) with pHPT and coexistent 25-hydroxyvitamin D deficiency (25OHD ≤50 nmol/l (≤20 ng/ml)). Patients who showed an increase in serum 25OHD above the threshold of vitamin D deficiency (>50 nmol/l; n=28) using treatment with various commonly prescribed vitamin D preparations were, for the purposes of statistical analyses, allocated to the treatment group. Patients who were retrospectively identified as having received no treatment with vitamin D and/or remained vitamin D deficient were considered as non-responders/controls (n=12). Adjusted calcium (adjCa), PTH and 25OHD concentrations were monitored in all subjects up to 54 months (mean observation period of 18±2 months). Results: Prolonged increased vitamin D intake, regardless of the source (serum 25OHD, increase from 32.2±1.7 nmol/l at baseline to 136.4±11.6 nmol/l, P0.73). In contrast, serum PTH remained unchanged (15.8±2.6 vs 16.3±1.9 pmol/l, P=0.64) in patients who remained vitamin D deficient, with a significant difference between groups in changes of PTH (P=0.0003). Intrapartial correlation analyses showed an independent negative correlation of changes in 25OHD with PTH levels (r ic=−0.41, P=0.014). Conclusions: Prolonged treatment with vitamin D in various commonly prescribed preparations appeared to be safe and significantly reduced PTH levels by 21%

Laryngeal Dysplasia and narrow band imaging: secondary analysis of published data supports the role in patient follow up

Background: Clinicians have recognised the role of narrow band imaging (NBI) in the management of head and neck cancer in several studies. However, a recent systematic review was unable to pool the data on diagnostic efficacy in this setting owing to the heterogeneity in the published data. Methods: Secondary analysis of data, utilising Bayes’ theorem, from meta‐analyses and randomised trials Results: In patients with a histological diagnosis of mild dysplasia who show no abnormalities on NBI, the post‐test probability of malignancy is 2.3%, compared to 10.3% with conventional white light imaging (WLI). For severe dysplasia, similar post‐test probabilities after NBI and WLI are 8.0% and 29.7% respectively. Post‐test probabilities in this setting indicate the chance of missing malignancy following a negative NBI or WLI in patients who undergo no further intervention. This paper also provides a nomogram designed for use in this setting. Conclusions: This paper identifies the evidence base for use of NBI in the follow up for laryngeal dysplasia

Second-look PET-CT following an initial incomplete PET-CT response to (chemo)radiotherapy for head and neck squamous cell carcinoma

OBJECTIVES: The limited positive predictive value of an incomplete response on PET-CT following (chemo)radiotherapy for head and neck squamous cell carcinoma (HNSCC) means that the optimal management strategy remains uncertain. The aim of the study is to assess the utility of a 'second-look' interval PET-CT. METHODS: Patients with HNSCC who were treated with (chemo)radiotherapy between 2008 and 2017 and underwent (i) baseline and (ii) response assessment PET-CT and (iii) second-look PET-CT following incomplete (positive or equivocal scan) response were included. Endpoints were conversion rate to complete response (CR) and test characteristics of the second-look PET-CT. RESULTS: Five hundred sixty-two patients with HNSCC underwent response assessment PET-CT at a median of 17 weeks post-radiotherapy. Following an incomplete response on PET-CT, 40 patients underwent a second-look PET-CT at a median of 13 weeks (range 6-25) from the first response PET-CT. Thirty-four out of 40 (85%) patients had oropharyngeal carcinoma. Twenty-four out of 40 (60%) second-look PET-CT scans converted to a complete locoregional response. The primary tumour conversion rate was 15/27 (56%) and the lymph node conversion rate was 14/19 (74%). The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the second-look PET-CT were 75%, 75%, 25% and 96% for the primary tumour and 100%, 92%, 40% and 100% for lymph nodes. There were no cases of progression following conversion to CR in the primary site or lymph nodes. CONCLUSIONS: The majority of patients who undergo a second-look PET-CT convert to a CR. The NPV of a second-look PET-CT is high, suggesting the potential to avoid surgical intervention. KEY POINTS: • PET-CT is a useful tool for response assessment following (chemo)radiotherapy for head and neck squamous cell carcinoma. • An incomplete response on PET-CT has a limited positive predictive value and optimal management is uncertain. • These data show that with a 'second-look' interval PET-CT, the majority of patients convert to a complete metabolic response. When there is doubt about clinical and radiological response, a 'second-look' PET-CT can be used to spare patients unnecessary surgical intervention

Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocol.

INTRODUCTION:Patients with head and neck squamous cell carcinoma with locally advanced disease often require multimodality treatment with surgery, radiotherapy and/or chemotherapy. Adjuvant radiotherapy with concurrent chemotherapy is offered to patients with high-risk pathological features postsurgery. While cure rates are improved, overall survival remains suboptimal and treatment has a significant negative impact on quality of life.Cell cycle checkpoint kinase inhibition is a promising method to selectively potentiate the therapeutic effects of chemoradiation. Our hypothesis is that combining chemoradiation with a WEE1 inhibitor will affect the biological response to DNA damage caused by cisplatin and radiation, thereby enhancing clinical outcomes, without increased toxicity. This trial explores the associated effect of WEE1 kinase inhibitor adavosertib (AZD1775). METHODS AND ANALYSIS:This phase I dose-finding, open-label, multicentre trial aims to determine the highest safe dose of AZD1775 in combination with cisplatin chemotherapy preoperatively (group A) as a window of opportunity trial, and in combination with postoperative cisplatin-based chemoradiation (group B).Modified time-to-event continual reassessment method will determine the recommended dose, recruiting up to 21 patients per group. Primary outcomes are recommended doses with predefined target dose-limiting toxicity probabilities of 25% monitored up to 42 days (group A), and 30% monitored up to 12 weeks (group B). Secondary outcomes are disease-free survival times (groups A and B). Exploratory objectives are evaluation of pharmacodynamic (PD) effects, identification and correlation of potential biomarkers with PD markers of DNA damage, determine rate of resection status and surgical complications for group A; and quality of life in group B. ETHICS AND DISSEMINATION:Research Ethics Committee, Edgbaston, West Midlands (REC reference 16/WM/0501) initial approval received on 18/01/2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBER:ISRCTN76291951 and NCT03028766

Association between loss of Y chromosome and poor prognosis in male head and neck squamous cell carcinoma

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is more prevalent in men than women and this disparity cannot be fully explained by known risk factors. Recent studies have shown that loss of Y chromosome (LoY) confers an increased risk of solid cancer and reduces life expectancy in men. METHODS: Using publicly available data from The Cancer Genome Atlas, we investigated the prevalence of LoY and its association with clinicopathological features in male HNSCC. RESULTS: LoY was detectable in around 25% of male HNSCC. Men with human papillomavirus-negative tumors exhibiting LoY experienced significantly worse overall survival than those with no LoY. Moreover, LoY tumors exhibited overexpression of genes involved in redox processes, including genes previously implicated in resistance to both radiotherapy and cisplatin-based chemotherapeutics. CONCLUSION: LoY may be an indicator of poor prognosis in male HNSCC that is linked to the overexpression of genes associated with resistance to standard care therapies