Search

Funder: UCLH Biomedical Research Centre, 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.

TP53 mutations are considered a surrogate biomarker of the serous‐like ‘copy number high’ molecular subtype of endometrial carcinoma (EC). In ovarian carcinoma, p53 immunohistochemistry (IHC) accurately reflects mutational status with almost 100% specificity but its performance in EC has not been established. This study tested whether p53 IHC reliably predicts TP53 mutations identified by next‐generation sequencing (NGS) in EC biopsy samples for all ECs and as part of a molecular classification algorithm after exclusion of cases harbouring mismatch repair defects (MMRd) or pathogenic DNA polymerase epsilon exonuclease domain mutations (POLE mut). A secondary aim assessed inter‐laboratory variability in p53 IHC. From a total of 207 cases from five centres (37–49 cases per centre), p53 IHC carried out at a central reference laboratory was compared with local IHC (n = 164) and curated tagged‐amplicon NGS TP53 sequencing results (n = 177). Following consensus review, local and central p53 IHC results were concordant in 156/164 (95.1%) tumours. Discordant results were attributable to both interpretive and technical differences in staining between the local and central laboratories. When results were considered as any mutant pattern versus wild‐type pattern staining, however, there was disagreement between local and central review in only one case. The concordance between p53 IHC and TP53 mutation was 155/168 (92.3%) overall, and 117/123 (95.1%) after excluding MMRd and POLE mut EC. Three (3/6) discordant results were in serous carcinomas with complete absence of p53 staining but no detectable TP53 mutation. Subclonal mutant p53 IHC expression was observed in 9/177 (5.1%) cases, of which four were either MMRd or POLE mut. Mutant pattern p53 IHC was observed in 63/63 (100%) serous carcinomas that were MMR‐proficient/POLE exonuclease domain wild‐type. Optimised p53 IHC performs well as a surrogate test for TP53 mutation in EC biopsies, demonstrates excellent inter‐laboratory reproducibility, and has high clinical utility for molecular classification algorithms in EC., This project was funded by a research grant from Barts and the London Charity, MRD0206, supported by the Gynaecological Cancer Research Fund at Barts and the London NHS Trust. We would like to acknowledge the support of Mr Ranjit Manchanda and Mr AR Jeyarajah, Consultant Gynaecological Oncologists, Barts Health NHS Trust, for their support of this project.

Background The serum biomarker cancer antigen 125 (CA125) is widely used as an investigation for possible ovarian cancer in symptomatic women presenting to primary care. However, its diagnostic performance in this setting is unknown. We evaluated the performance of CA125 in primary care for the detection of ovarian and non-ovarian cancers. Methods and findings We studied women in the United Kingdom Clinical Practice Research Datalink with a CA125 test performed between 1 May 2011–31 December 2014. Ovarian and non-ovarian cancers diagnosed in the year following CA125 testing were identified from the cancer registry. Women were categorized by age, Garth Funston and colleagues assess the diagnostic efficacy of CA125 for ovarian cancer detection, Author summary Why was this study done? CA125 is widely used as a test for ovarian cancer in women presenting with relevant symptoms, both in the UK and internationally. CA125 has been extensively evaluated in the specialist care setting and in screening studies but little was known about its diagnostic performance in primary care, where most patients with ovarian cancer first present. What did the researchers do and find? We evaluated the diagnostic performance of CA125 in 50,780 women undergoing testing in English general practice. Of women with CA125 levels above the current abnormal cut-off, 10.1% were diagnosed with ovarian cancer and a further 12.3% with another form of cancer. Cancer was more common in women with abnormal CA125 levels if they were ≥50 years of age. We developed models to estimate the probability of ovarian cancer and all cancer based on a woman’s age and CA125 level. What do these findings mean? Clinicians should consider the possibility of non-ovarian cancer, in addition to ovarian cancer, in women with high CA125 levels. Our models will enable patients and clinicians to determine the estimated probability of cancer based on an individual’s age and CA125 level. This information can be used to help make decisions about the need for further investigation or urgent referral to a specialist. The findings should also help inform guidelines, as they will allow recommendations for further testing to be made on the basis cancer probability rather than a single CA125 cutoff.