Screening and testing practices for Lynch syndrome in Nova Scotians with endometrial cancer: a descriptive study.

BACKGROUND: Identifying people with Lynch syndrome, a genetic condition predisposing those affected to colorectal, endometrial and other cancers, allows for implementation of risk-reducing strategies for patients and their families. The goal of this study was to describe screening and testing practices for this condition among people with endometrial cancer in Nova Scotia, Canada, and to determine the prevalence of Lynch syndrome in this population. METHODS: All patients diagnosed with endometrial cancer in Nova Scotia between May 1, 2017, and Apr. 30, 2020 were identified through a provincial gynecologic oncology database. Patients from out of province were excluded. We collected age, body mass index, tumour mismatch repair protein immunohistochemistry results, personal and family histories, and germline testing information for all patients. RESULTS: We identified 465 people diagosed with endometrial cancer during the study period. Most were aged 51 years or older, and had obesity and low-grade early-stage endometrioid tumours. Tumour immunohistochemistry testing was performed in 444 cases (95.5%). Based on local criteria, 189 patients were eligible for genetic counselling, of whom 156 (82.5%) were referred to medical genetics. Of the 98 patients who underwent germline testing, 9 (9.2%) were diagnosed with Lynch syndrome. INTERPRETATION: The prevalence of Lynch syndrome was at least 1.9% (9/465) in this population. Our results illustrate successful implementation of universal tumour testing; however, there remains a gap in access to genetic counselling.

Hereditary ovarian cancer risk reduction: a retrospective evaluation of patient perspectives and service provision at a regional hereditary gynaecologic cancer clinic 2006-2016.

BACKGROUND: Germline pathogenic variants in BRCA1/2 have been established in hereditary breast and ovarian cancer (HBOC) syndrome and result in significantly elevated lifetime risk of ovarian cancer. Risk reduction interventions are presently the only effective means of improving survival and specialized counselling clinics have been established as an effective means of aiding this population in navigating complex decisions surrounding these interventions. This study sought to evaluate patient perceptions of a specialized counselling clinic for patients with HBOC Syndrome and referral patterns to this clinic. METHODS: We completed a retrospective review of 200 patients with HBOC in Nova Scotia, Canada seen through Maritime Medical Genetics Services between 2006 and 2016. Data were collected on referral pattern to the Hereditary Gynaecologic Risk Reduction Clinic (HGRRC), demographics, health history, and uptake of risk-reducing interventions. Participants were invited to complete a questionnaire about their experience. RESULTS: 156/200(78%) women were referred to HGRCC and 135/156 (85.9%) of those referred attended their appointment. 124/200 (62%) were over age 40 at the time of testing. The mean time from referral to HGRCC appointment was 134.68 days (SD 85.78). 85/135 (63%) underwent risk-reducing bilateral salpingo-oophorectomy following their HGRCC appointment. The questionnaire was completed by 94/188 (50.3%) women. Most participants found information received from genetics clinics (81/94; 91%) and genetic counsellors (87/94; 95%) most helpful in making choices around risk-reduction strategies. 83/94 (88%) participants felt they had sufficient information to make an informed decision. CONCLUSION: The majority of women with HBOC in Nova Scotia during the study period were referred to and counselled through HGRRC. Genetic counselling was found most valuable in risk-reduction decision making, which highlights the importance of a multidisciplinary team. Patients viewed this clinic as an effective care model to support informed choice about risk-reducing intervention.

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Universal access to genetic counseling for women with epithelial ovarian cancer in Nova Scotia: Evaluating a new collaborative care model.

Women with pathogenic variants in BRCA1/2 have a significantly increased lifetime risk of breast and ovarian cancers. The availability of genetic testing to identify BRCA1/2 carriers is imperative to disease prevention and treatment. We evaluated the effectiveness of a new collaborative care model in Nova Scotia, involving the integration of genetic counselors into tumor board rounds, reduction in time allotted for initial genetic counseling appointments from 60 to 45 min, and a standardized dictation template, to increase referral rate for genetic counseling. We also assessed the study cohorts' preferences on timing for genetic testing. A retrospective chart review was performed on all women diagnosed with epithelial ovarian cancer (EOC) from 2012 to 2017 (N = 386). Pertinent clinical outcomes were categorized and wait times to different nodes of the clinical pathway assessed. A questionnaire was sent to this same cohort of women to identify preference for the timing of genetic testing (n = 103). The chi-square and Wilcoxon's rank-sum tests were used to compare demographic and clinical variables pre- and post-care model implementation. We identified a 48.2% (95% CI: 39.4-56.7, p < .001) increase in referral for genetic counseling following implementation of the new care model. Median time from diagnosis to referral decreased by 74.0 days (p < .001) and median time from referral to first appointment by 54.0 days (p < .001). 56.3% of women desired referral at the time of diagnosis. This care model for women newly diagnosed with EOC in Nova Scotia was successful in increasing referral rates for genetic counseling. Majority of women pursued genetic testing following and favored that referral for genetic counseling be made at the time of diagnosis, highlighting the importance for timely access.

Evolution of genetic assessment for BRCA-associated gynaecologic malignancies: a Canadian multisociety roadmap.

The landscape of genetic testing in ovarian cancer patients has changed dramatically in recent years. The therapeutic benefits of poly ADP-ribose polymerase (PARP) inhibitors in treatment of BRCA1/2-related ovarian cancers has resulted in an increased demand and urgency for genetic testing results, while technological developments have led to widespread use of multi-gene cancer panels and development of tumour testing protocols. Traditional genetic counselling models are no longer sustainable and must evolve to match the rapid evolution of genetic testing technologies and developments in personalized medicine. Recently, representatives from oncology, clinical genetics, molecular genetics, pathology, and patient advocacy came together to create a national multi-disciplinary Canadian consortium. By aligning stakeholder interests, the BRCA Testing to Treatment (BRCA TtoT) Community of Practice aims to develop a national strategy for tumour and germline BRCA1/2 testing and genetic counselling in women with ovarian cancer. This article serves to provide an overview of the recent evolution of genetic assessment for BRCA1/2-associated gynecologic malignancies and outline a Canadian roadmap to facilitate change, improve genetic testing rates, and ultimately improve outcomes for hereditary ovarian cancer patients and their families.

Malignant Struma ovarii in a 30-year old nulliparous patient.

BACKGROUND: Struma ovarii is a rare monodermal germ cell tumor where the ovary is comprised of at least half thyroid tissue. This phenomenon may indicate an embryological origin. CASE PRESENTATION: A 30-year old nulliparous woman presented with acute right lower quadrant pain and underwent laparoscopic right salpingo-oophorectomy. The excised ovarian mass showed evidence of struma-derived papillary thyroid carcinoma. Ultrasound of the thyroid showed mild enlargement with two solid nodules. A fine needle aspirate of a thyroid nodule was positive for malignancy and a total thyroidectomy was performed. Microscopic features of the thyroid were consistent with papillary thyroid carcinoma. The two tumours were considered as synchronous independent primaries based on their histological presentation. CONCLUSIONS: We believe that aggressive surgical management followed by radioiodine therapy is best to reduce recurrence risk and optimize survival. The broad scope of interventions needed to treat malignant struma ovarii require a strong interdisciplinary team.

Choosing the right patient: planning for laparotomy or laparoscopy in the patient with endometrial cancer.

OBJECTIVE: Endometrial cancer remains the most commonly diagnosed gynaecologic cancer in North America. The staging and initial treatment of endometrial cancer involves surgery. Laparoscopic surgery is increasingly used as an alternative to laparotomy. Patient selection for laparoscopy can be optimized by examining factors involved in both the choice of surgical approach and the ultimate procedure performed. We wished to identify factors that might be barriers to laparoscopic surgery in women with endometrial cancer who had surgery performed by the gynaecologic oncology group at the Capital District Health Authority (CDHA) in Halifax, Nova Scotia. METHODS: We conducted a retrospective review of the records of women with endometrial cancer, histologically confirmed preoperatively between 2005 and 2007, who underwent surgery at the CDHA. RESULTS: Between 2005 and 2007 in Nova Scotia, 428 cases of endometrial cancer were diagnosed, and 289 women with a preoperative diagnosis of endometrial cancer underwent surgery at the CDHA. Of these, 66.1% (191/289) underwent a planned laparotomy, and 33.9% (98/289) had a planned laparoscopy. The proportion of attempted laparoscopies increased from 21.9% to 57.1% (P = 0.002) over time, while there was no change in the conversion rate (P = 0.23). Patients with abnormal findings on pelvic examination were more likely to have a laparotomy (RR = 1.5; 95% CI 1.34 to 1.68). Independent predictors of laparoscopic conversion to laparotomy were age 75 years or over (P = 0.03) and non-endometrioid histology (P = 0.002). CONCLUSION: Our data identify age and non-endometrioid histology as independent factors for conversion of surgery for endometrial cancer from laparoscopy to laparotomy. With this information we can optimize patient selection for laparoscopic surgery. Patients undergoing a conversion to laparotomy do not have a significant increase in surgery time or perioperative morbidity.

Hereditary breast ovarian cancer syndromes in the Maritimes.

OBJECTIVES: The purpose of this study was to characterize the population referred to the Maritime Medical Genetics Service (MMGS) because of increased risk of breast and/or ovarian cancer, and to evaluate the MMGS referral criteria for this population. METHODS: We reviewed a retrospective cohort of patients at increased risk of breast and/or ovarian cancer (n = 574) with appointments between January 2001 and May 2007 at the MMGS. Data analysis was performed using descriptive statistics in Filemaker Pro 8.5v1 and Microsoft Excel. RESULTS: Among 574 patients, 253 (44%) had test results available at the time of data collection, and 65 (25.7%) had BRCA mutations (44 BRCA1 and 21 BRCA2). Positive test results for each referral criterion ranged from 0% to 100%. CONCLUSION: Use of referral criteria at the MMGS yielded higher rates of positive test results than previously thought. It may be beneficial to expand testing criteria to ensure that everyone who may carry a mutation is offered testing.

Risk of malignancy index in the evaluation of patients with adnexal masses.

OBJECTIVE: To determine if the risk of malignancy index (RMI) can distinguish between benign and malignant adnexal masses in a population of women referred to a department of gynaecologic oncology for surgical resection of an adnexal mass. METHODS: We performed a retrospective review of the medical of charts of 259 consecutive patients. Ninety-six charts did not have data available to calculate the RMI, leaving a total of 163 for review. Three definitions of RMI were compared; each incorporated menopausal status of the patient, ultrasound characteristics of the adnexal mass, and serum CA-125 level. RESULTS: Of the masses resected, 105 were benign and 58 were malignant. The area under the ROC curve for all three definitions of RMI was 0.87. Using a cut-off of 120, the first RMI definition (RMI 1) had a sensitivity of 72% and a specificity of 87%; the second (RMI 2) had a sensitivity of 76% and a specificity of 81%; and the third (RMI 3) had a sensitivity of 74% and a specificity of 84%. These results are generally in agreement with published values. CONCLUSION: We have validated the use of RMI to predict the risk of malignancy in a Nova Scotia population of women with adnexal masses. This will aid in more selective referral of patients to specialized oncology centres for cancer surgery, allowing for appropriate management of health care resources and optimization of treatment for women with gynaecological malignancies.

Who should operate on patients with ovarian cancer? An evidence-based review.

OBJECTIVE: To evaluate the relationship between surgical specialty and survival in patients receiving initial surgical management for ovarian epithelial cancer. STUDY METHODS: An analytic framework was constructed to address the principle question 'does the type of surgeon operating on patients with newly diagnosed ovarian epithelial cancer influence survival?' A literature search addressing the components of this analytic framework was carried out using the Cochrane Library, Medline, EMBASE, and HealthSTAR databases. Relevant articles were selected and graded using U.S. Preventive Services Task Force and Canadian Task Force guidelines. Results were summarized by quality as well as level of evidence. RESULTS: Eighteen studies were reviewed. The quality of evidence was good in 3, fair in 8, and poor in 7 of the studies. The most common study flaws encountered were 'failure to account for confounders' and 'incompleteness of data'. In studies focusing on advanced disease, there was good quality evidence to support a 6- to 9-month median survival benefit for patients operated on by gynecologic oncologists rather than general gynecologists and/or general surgeons (P values 0.009 to 0.01). Studies focusing on early stage disease found gynecologic oncologists more likely to carry out optimal staging (P values 0.001 to 0.01). Increased survival could be explained by improved identification of true stage I patients. CONCLUSION: Patients receiving initial surgical management for ovarian epithelial cancer should be operated on by gynecologic oncologists.

What's new in systemic therapy for endometrial cancer.

PURPOSE OF REVIEW: Endometrial cancer is one of the most common gynecologic cancers. Most women present with early disease that is curable. In women with poor prognostic factors or advanced disease, survival is greatly diminished. Recently there have been several trials of adjuvant treatment and treatment for advanced and recurrent endometrial cancer. These trials of systemic therapy will be reviewed. RECENT FINDINGS: Several areas have been the focus of recent literature on systemic therapy for endometrial cancer. These include large phase III trials of multi-agent chemotherapy regimens for advanced and recurrent endometrial cancer, combined chemotherapy and radiotherapy treatments, and novel targeted agents. SUMMARY: New approaches to combining the traditional adjuvant modalities for high-risk endometrial cancer as well as combining new novel agents with traditional chemotherapeutics will improve patient outcomes.