Positive experiences of healthcare professionals with a mainstreaming approach of germline genetic testing for women with ovarian cancer

According to current guidelines, all women with epithelial ovarian cancer are eligible for genetic testing for BRCA germline pathogenic variants. Unfortunately, not all affected women are tested. We evaluated the acceptability and feasibility for non-genetic healthcare professionals to incorporate germline genetic testing into their daily practice. We developed and implemented a mainstreaming pathway, including a training module, in collaboration with various healthcare professionals and patient organizations. Healthcare professionals from 4 different hospitals were invited to participate. After completing the training module, gynecologic oncologists, gynecologists with a subspecialty training in oncology, and nurse specialists discussed and ordered genetic testing themselves. They received a questionnaire before completing the training module and 6 months after working according to the new pathway. We assessed healthcare professionals' attitudes, perceived knowledge, and self-efficacy, along with the feasibility of this new mainstream workflow in clinical practice, and evaluated the use and content of the training module. The participation rate for completing the training module was 90% (N = 19/21). At baseline and after 6 months, healthcare professionals had a positive attitude, high perceived knowledge and high self-efficacy toward discussing and ordering genetic testing. Knowledge had increased significantly after 6 months. The training module was rated with an average of 8.1 out of 10 and was considered useful. The majority of healthcare professionals (9/15) was able to discuss a genetic test in five to 10 min. After completion of a training module, non-genetic healthcare professionals feel motivated and competent to discuss and order genetic testing themselves.Hereditary cancer genetic

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

Background:It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis.Methods:We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC.Results:BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HR mult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HR mult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HR mult 1.15; 95% CI 0.84-1.57) and OCSS (HR mult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HR mult 1.99; 95% CI 1.21-3.31).Conclusions:Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy

Short-term surgical complications after radical hysterectomy—A nationwide cohort study

Introduction: Centralization has, among other aspects, been argued to have an impact on quality of care in terms of surgical morbidity. Next, monitoring quality of care is essential in identifying areas of improvement. This nationwide cohort study was conducted to determine the rate of short-term surgical complications and to evaluate its possible predictors in women with early-stage cervical cancer. Material and methods: Women diagnosed with early-stage cervical cancer, 2009 FIGO stages IB1 and IIA1, between 2015 and 2017 who underwent radical hysterectomy with pelvic lymphadenectomy in 1 of the 9 specialized medical centers in the Netherlands, were identified from the Netherlands Cancer Registry. Women were excluded if primary treatment consisted of hysterectomy without parametrial dissection or radical trachelectomy. Women in whom radical hysterectomy was aborted during the procedure, were also

The Feasibility of Implementing Mainstream Germline Genetic Testing in Routine Cancer Care-A Systematic Review

BACKGROUND: Non-genetic healthcare professionals can provide pre-test counseling and order germline genetic tests themselves, which is called mainstream genetic testing. In this systematic review, we determined whether mainstream genetic testing was feasible in daily practice while maintaining quality of genetic care. METHODS: PubMed, Embase, CINAHL, and PsychINFO were searched for articles describing mainstream genetic testing initiatives in cancer care. RESULTS: Seventeen articles, reporting on 15 studies, met the inclusion criteria. Non-genetic healthcare professionals concluded that mainstream genetic testing was possible within the timeframe of a routine consultation. In 14 studies, non-genetic healthcare professionals completed some form of training about genetics. When referral was coordinated by a genetics team, the majority of patients carrying a pathogenic variant were seen for post-test counseling by genetic healthcare professionals. The number of days between cancer diagnosis and test result disclosure was always lower in the mainstream genetic testing pathway than in the standard genetic testing pathway (e.g., pre-test counseling at genetics department). CONCLUSIONS: Mainstream genetic testing seems feasible in daily practice with no insurmountable barriers. A structured pathway with a training procedure is desirable, as well as a close collaboration between genetics and other clinical departments

Vaginal Radical Trachelectomy for Early-Stage Cervical Cancer: Increased Recurrence Risk for Adenocarcinoma

OBJECTIVE: To evaluate consecutive vaginal radical trachelectomies (VRTs) in early-stage cervical cancer in the 2 main referral centers for fertility-preserving surgery in the Netherlands. MATERIALS AND METHODS: Oncology, fertility, and obstetrical data were recorded in a regional database of all VRTs without neoadjuvant chemotherapy performed in 2 major referral centers between 2000 and 2015. RESULTS: Most of the patients (91.7%) had stage IB1 disease. In 72.0%, squamous cell carcinoma was the histologic diagnosis; in 24.2%, adenocarcinoma; and in 3.8%, adenosquamous carcinoma. The median follow-up was 51 months.Nine (6.8%) recurrences occurred, 4 resulting in death of disease (death rate, 3.0%). Recurrence rates were 12.5% for adenocarcinoma, 20% for adenosquamous carcinoma, and 4.2% for squamous cell carcinoma (P < 0.01).From 117 women, data about fertility and obstetrical outcome were obtained. Almost 60% of women attempted to conceive after a VRT. Of these women, 40% needed fertility treatment. A total of 47 pregnancies were established, and a total of 37 children were born of which 30 (81.1%) were delivered after 32 weeks of gestational age. CONCLUSIONS: Nonsquamous cell histology and high-grade disease are associated with a significantly higher risk of recurrence in the univariate and multivariate analyses. Women with both these histology features should be counseled reticently for VRT.Pregnancies after VRT must be regarded as high-risk pregnancies with a high prematurity rate

Methylation profiles of endometrioid and serous endometrial cancers.

Item does not contain fulltextPromoter methylation is a gene- and cancer type-specific epigenetic event that plays an important role in tumour development. As endometrioid (endometrioid endometrial carcinoma, EEC) and serous endometrial cancers (uterine papillary serous carcinoma, UPSC) exhibit different clinical, histological and molecular genetic characteristics, we hypothesized that these differences may be reflected in epigenetic phenomena as well. Identification of a panel of methylation biomarkers could be helpful in a correct histological classification of these two subtypes, which solely on the basis of morphology is not always easy. Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of different tumour suppressor genes in EEC and UPSC. Methylation results were correlated with histology and survival. The median cumulative methylation index of all genes was significantly higher in EEC (124) than in UPSC (93) (P<0.001). Promoter methylation of CDH13 and MLH1 was more frequently present in EEC, while CDKN2B and TP73 were more frequently methylated in UPSC. Almost 90% of EEC and 70% of UPSC could be predicted by CDH13 and TP73. In EEC, methylation of MLH1 was associated with a shorter disease-free survival (DFS; P<0.0001) and overall survival (OS; P=0.005). In a multivariate model, MLH1 methylation emerged as an additional prognostic factor to stage for DFS (P=0.002). In conclusion, promoter methylation is more common in EEC than UPSC. A panel of methylation biomarkers could be useful to distinguish between the two histological subtypes of endometrial cancer. Furthermore, methylation of MLH1 may have prognostic value in EEC

Differences between hereditary and sporadic ovarian cancer

Approximately 5% of ovarian cancer cases can be attributed to an autosomal dominant inheritance factor. The majority of these cases are due to germline mutations in the BRCA1 or BRCA2 tumoursupressor genes. Patients with hereditary disease do not exhibit pathognomonic features that would allow distinction from non-hereditary (sporadic) cases of ovarian cancer. Our studies are aimed at identifying clinical, histopathological as well as molecular genetic differences between hereditary and sporadic ovarian cancer. Clinical studies of the ovarian cancer cases in 31 families revealed differences regarding age at onset and stage as well as in survival compared with cancer registry controls. The molecular studies of hereditary ovarian cancer are still underway and some preliminary data is discussed

Characteristics of Lynch syndrome associated ovarian cancer

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Identifying patients with a history of ovarian cancer for referral for genetic counselling: non-randomised comparison of two case-finding strategies in primary care.

Item does not contain fulltextBACKGROUND: Recent guidelines recommend genetic counselling and DNA testing (GCT) for patients with ovarian cancer and survivors of ovarian cancer. Finding survivors of ovarian cancer is challenging. Detecting and referring them for GCT via primary care, to allow proper screening recommendations for patients and their family, may be a solution. AIM: To compare the effectiveness and acceptance of two pilot strategies directed at case finding women with a history of ovarian cancer for referral for GCT by their GP. DESIGN AND SETTING: Non-randomised comparison of the pilot implementation of two case-finding strategies for women with a history of ovarian cancer in Dutch primary care from May 2016 to April 2017. METHOD: Strategy A (unsupported) asked GPs to identify and refer eligible patients with a history of ovarian cancer. Strategy B (ICT-supported) provided GPs with information and communication technology (ICT) support to identify patients with a history of ovarian cancer electronically. The effectiveness of each strategy was assessed as the proportion of patients who were approached, referred for GCT, and seen by the clinical geneticist. Acceptance of each strategy was assessed by the intervention uptake of GP practices and GP and patient questionnaires. RESULTS: Nineteen out of 30 (63%) patients identified with a history of ovarian cancer were deemed eligible for referral for strategy A, and 39 out of 94 (41%) for strategy B. For each strategy, eight patients were referred and five (63%) were seen for GCT. The intervention uptake by GP practices was 31% (11 out of 36) for strategy A and 46% (21 out of 46) for strategy B. GPs considered 'relevance' and 'workability' as facilitators across both strategies whereas, for strategy B, technical barriers hindered implementation. CONCLUSION: The effectiveness and acceptance of both strategies for case finding of survivors of ovarian cancer in primary care for GCT is promising, but larger studies are required before wide-scale implementation is warranted.1 november 201