The most efficient and effective BRCA1/2 testing strategy in epithelial ovarian cancer:Tumor-First or Germline-First?

Objective: Genetic testing in epithelial ovarian cancer (OC) is essential to identify a hereditary cause like a germline BRCA1/2 pathogenic variant (PV). An efficient strategy for genetic testing in OC is highly desired. We evaluated costs and effects of two strategies; (i) Tumor-First strategy, using a tumor DNA test as prescreen to germline testing, and (ii) Germline-First strategy, referring all patients to the clinical geneticist for germline testing.Methods: Tumor-First and Germline-First were compared in two scenarios; using real-world uptake of testing and setting implementation to 100%. Decision analytic models were built to analyze genetic testing costs (including counseling) per OC patient and per family as well as BRCA1/2 detection probabilities. With a Markov model, the life years gained among female relatives with a germline BRCA1/2 PV was investigated.Results: Focusing on real-world uptake, with the Tumor-First strategy more OC patients and relatives with a germline BRCA1/2 PV are detected (70% versus 49%), at lower genetic testing costs (€1898 versus €2502 per patient, and €2511 versus €2930 per family). Thereby, female relatives with a germline BRCA1/2 PV can live on average 0.54 life years longer with Tumor-First compared to Germline-First. Focusing on 100% uptake, the genetic testing costs per OC patient are substantially lower in the Tumor-First strategy (€2257 versus €4986).Conclusions: The Tumor-First strategy in OC patients is more effective in identifying germline BRCA1/2 PV at lower genetic testing costs per patient and per family. Optimal implementation of Tumor-First can further improve detection of heredity in OC patients.</p

Cost-effectiveness of sentinel lymph node biopsy vs inguinofemoral lymphadenectomy in women with vulval cancer

background: This study examines the cost-effectiveness of sentinel lymph node biopsy, a potentially less morbid procedure, compared with inguinofemoral lymphadenectomy (IFL) among women with stage I and stage II vulval squamous cell carcinoma. methods: A model-based economic evaluation was undertaken based on clinical evidence from a systematic review of published sources. A decision tree model was developed with the structure being informed by clinical input, taking the perspective of the health-care provider. results: For overall survival for 2 years, IFL was found to be the most cost-effective option and dominated all other strategies, being the least costly and most effective. For morbidity-free related outcomes for 2 years, sentinel lymph node (SLN) biopsy with 99mTc and blue dye and haematoxylin & eosin (H&E) histopathology, with ultrastaging and immunohistochemistry reserved for those that test negative following H&E is likely to be the most effective approach. conclusion: SLN biopsy using 99mTc and blue dye with ultrastaging may be considered the most cost-effective strategy based on the outcome of survival free of morbidity for 2 years. The findings here also indicate that using blue dye and H&E for the identification of the SLN and the identification of metastasis, respectively, are not sensitive enough to be used on their own

Genetic counseling of patients with ovarian carcinoma:acceptance, timing, and psychological wellbeing

The new Dutch guidelines on hereditary and familial ovarian carcinoma recommend genetic testing of all patients with epithelial ovarian cancer (EOC). With this study, we aimed to obtain insight into (1) the acceptance and timing of the offer of genetic counseling in women with EOC, (2) reasons for accepting or declining genetic counseling, and (3) psychological differences between women who did and did not have genetic counseling. A multicenter questionnaire survey was performed in patients with EOC in four Dutch oncology centers. The questionnaire addressed whether, how, and when genetic counseling was offered, women's arguments to accept or decline genetic counseling, and included the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). A total of 67 women completed the questionnaire, of which 43 had genetic counseling. Despite a wide variability in the timing of the offer of genetic counseling, 89% of the women were satisfied with the timing. No significant differences were found between the CWS and HADS scores for the timing of the offer of genetic counseling and whether or not women had genetic counseling. Taking the small sample size into account, the results tentatively suggest that genetic counseling may have limited impact on the psychosocial wellbeing of women with EOC. Therefore, we assume that implementation of the new guidelines offering genetic counseling to all patients with EOC will not cause considerable additional burden to these patients

Lessons learned from rapid environmental risk assessments for prioritization of alien species using expert panels

Limiting the spread and impacts of invasive alien species (IAS) on biodiversity and ecosystems has become a goal of global, regional and national biodiversity policies. Evidence based management of IAS requires support by risk assessments, which are often based on expert judgment. We developed a tool to prioritize potentially new IAS based on their ecological risks, socio-economic impact and feasibility of management using multidisciplinary expert panels. Nine expert panels reviewed scientific studies, grey literature and expert knowledge for 152 species. The quality assessment of available knowledge revealed a lack of peer-reviewed data and high dependency on best professional judgments, especially for impacts on ecosystem services and feasibility of management. Expert consultation is crucial for conducting and validating rapid assessments of alien species. There is still a lack of attention for systematic and methodologically sound assessment of impacts on ecosystem services and weighting negative and positive effects of alien species.Peer reviewe