Incidence and survival of soft tissue sarcoma in England between 2013 and 2017, an analysis from the National Cancer Registration and Analysis Service.

There is a paucity of population-based data detailing the incidence and survival of patients with soft tissue sarcoma (STS), in part due to the heterogeneity of disease and changes to classification. Here, the incidence and survival of all STS subtypes registered in England between 2013 and 2017 were analysed using cancer registry data held by the National Cancer Registration and Analysis Service. Age-standardised incidence rates were calculated per 1 000 000 using the 2013 European Standard Population. Net survival was computed using Brenner's alternative method, with the Ederer II estimator. Age-specific overall survival was assessed using Kaplan-Meier. The influence of age, sex, socioeconomic deprivation and diagnostic routes on survival was assessed using Cox proportional hazards modelling. In total, 19 717 patients were diagnosed with STS, an average of 3943 patients per year and representing approximately 0.8% of malignancies. The most common histological diagnoses were Gastrointestinal Stromal Tumours (GIST), leiomyosarcoma and undifferentiated sarcoma, accounting for 20.2%, 13.3% and 12.7% of all sarcomas, respectively. Five-year net survival for all malignant STS was 65.0%; and was lowest for patients with vascular tumours at 39%. Patients from most deprived cohorts had 23% greater chance of dying within 5 years than patients in least deprived areas. This population-based study has allowed us for the first time to define the incidence and survival rates of prevalent STS subtypes in England such as GIST, liposarcoma and leiomyosarcoma, as well as rare entities and groups with inferior outcome. This data is invaluable for service provision, benchmarking and addressing inequality.

Purification and characterization of the Lassa virus transmembrane domain.

Lassa virus (LASV) is the most prevalent arenavirus afflicting humans and has high potential to become a threat to global public health. The transmembrane domain (TM) of the LASV glycoprotein complex forms critical interactions with the LASV stable signal peptide that are important for the maturation and fusion activity of the virus. A further study of the structure-based molecular mechanisms is required to understand the role of the TM in the lifecycle of LASV in greater detail. However, it is challenging to obtain the TM in high quantity and purity due to its hydrophobic nature which results in solubility issues that makes it prone to aggregation in typical buffer systems. Here, we designed a purification and detergent screen protocol for the highly insoluble TM to enhance the yield and purity for structural studies. Based on the detergents tested, the TM had the highest incorporation in LMPG. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy were utilized to confirm the best detergent system for structural studies. Through CD spectroscopy, we were able to characterize the secondary structure of the TM as largely alpha-helical, while NMR spectroscopy showed a well-structured and stable TM in LMPG. From these results, LMPG was determined to be the optimal detergent for further structural studies.

Sample sizes of prediction model studies in prostate cancer were rarely justified and often insufficient.

OBJECTIVE: Developing clinical prediction models (CPMs) on data of sufficient sample size is critical to help minimize overfitting. Using prostate cancer as a clinical exemplar, we aimed to investigate to what extent existing CPMs adhere to recent formal sample size criteria, or historic rules of thumb of events per predictor parameter (EPP)≥10. STUDY DESIGN AND SETTING: A systematic review to identify CPMs related to prostate cancer, which provided enough information to calculate minimum sample size. We compared the reported sample size of each CPM against the traditional 10 EPP rule of thumb and formal sample size criteria. RESULTS: About 211 CPMs were included. Three of the studies justified the sample size used, mostly using EPP rules of thumb. Overall, 69% of the CPMs were derived on sample sizes that surpassed the traditional EPP≥10 rule of thumb, but only 48% surpassed recent formal sample size criteria. For most CPMs, the required sample size based on formal criteria was higher than the sample sizes to surpass 10 EPP. CONCLUSION: Few of the CPMs included in this study justified their sample size, with most justifications being based on EPP. This study shows that, in real-world data sets, adhering to the classic EPP rules of thumb is insufficient to adhere to recent formal sample size criteria.

A review of plan library approaches in adaptive radiotherapy of bladder cancer.

BACKGROUND: Large variations in the shape and size of the bladder volume are commonly observed in bladder cancer radiotherapy (RT). The clinical target volume (CTV) is therefore frequently inadequately treated and large isotropic margins are inappropriate in terms of dose to organs at risk (OAR); thereby making adaptive radiotherapy (ART) attractive for this tumour site. There are various methods of ART delivery, however, for bladder cancer, plan libraries are frequently used. MATERIAL AND METHODS: A review of published studies on plan libraries for bladder cancer using four databases (Pubmed, Science Direct, Embase and Cochrane Library) was conducted. The endpoints selected were accuracy and feasibility of initiation of a plan library strategy into a RT department. RESULTS: Twenty-four articles were included in this review. The majority of studies reported improvement in accuracy with 10 studies showing an improvement in planning target volume (PTV) and CTV coverage with plan libraries, some by up to 24%. Seventeen studies showed a dose reduction to OARs, particularly the small bowel V45Gy, V40Gy, V30Gy and V10Gy, and the rectal V30Gy. However, the occurrence of no suitable plan was reported in six studies, with three studies showing no significant difference between adaptive and non-adaptive strategies in terms of target coverage. In addition, inter-observer variability in plan selection appears to remain problematic. The additional resources, education and technology required for the initiation of plan library selection for bladder cancer may hinder its routine clinical implementation, with eight studies illustrating increased treatment time required. CONCLUSIONS: While there is a growing body of evidence in support of plan libraries for bladder RT, many studies differed in their delivery approach. The advent of the clinical use of the MRI-linear accelerator will provide RT departments with the opportunity to consider daily online adaption for bladder cancer as an alternate to plan library approaches.