Multiparametric MRI radiomics for predicting disease-free survival and high-risk histopathological features for tumor recurrence in endometrial cancer.

Background: Current preoperative imaging is insufficient to predict survival and tumor recurrence in endometrial cancer (EC), necessitating invasive procedures for risk stratification. Purpose: To establish a multiparametric MRI radiomics model for predicting disease-free survival (DFS) and high-risk histopathologic features in EC. Methods: This retrospective study included 71 patients with histopathology-proven EC and preoperative MRI over a 10-year period. Clinicopathology data were extracted from health records. Manual MRI segmentation was performed on T2-weighted (T2W), apparent diffusion coefficient (ADC) maps and dynamic contrast-enhanced T1-weighted images (DCE T1WI). Radiomic feature (RF) extraction was performed with PyRadiomics. Associations between RF and histopathologic features were assessed using logistic regression. Associations between DFS and RF or clinicopathologic features were assessed using the Cox proportional hazards model. All RF with univariate analysis p-value < 0.2 were included in elastic net analysis to build radiomic signatures. Results: The 3-year DFS rate was 68% (95% CI = 57%-80%). There were no significant clinicopathologic predictors for DFS, whilst the radiomics signature was a strong predictor of DFS (p<0.001, HR 3.62, 95% CI 1.94, 6.75). From 107 RF extracted, significant predictive elastic net radiomic signatures were established for deep myometrial invasion (p=0.0097, OR 4.81, 95% CI 1.46, 15.79), hysterectomy grade (p=0.002, OR 5.12, 95% CI 1.82, 14.45), hysterectomy histology (p=0.0061, OR 18.25, 95% CI 2.29,145.24) and lymphovascular space invasion (p<0.001, OR 5.45, 95% CI 2.07, 14.36). Conclusion: Multiparametric MRI radiomics has the potential to create a non-invasive a priori approach to predicting DFS and high-risk histopathologic features in EC.

Management of inguinal lymph nodes in locally advanced, surgically unresectable, squamous cell carcinoma of the vulva.

OBJECTIVE: To assess clinical outcomes of inguinal lymph node surgical resection compared to primary groin radiotherapy for locally advanced, surgically unresectable vulvar cancer. METHODS: All patients treated with radiation for vulvar cancer were identified between Jan 1, 2000 - Dec 31, 2020 at 2 academic centres. Inclusion criteria were those treated with curative intent primary radiotherapy +/- chemotherapy, tumors >4 cm, and surgically unresectable squamous cell vulvar carcinoma. Groin recurrence-free survival (RFS) was compared for groin surgery and primary groin radiotherapy using the Kaplan Meier method and log rank test. Groin failures are described by treatment modality, radiation dose and lymph node size. RESULTS: Of 476 patients treated with radiation for vulvar cancer, 112 patients (23.5%) met inclusion and exclusion criteria. The median (95% CI) follow up was 1.9 (1.4-2.5) years. Complete clinical response was significantly higher (80.0%) in patients with surgical groin resection compared to patients treated with primary groin radiotherapy (58.2%) (p = 0.04). On multivariable analysis, after adjusting for clinical and/or radiologically abnormal lymph nodes (p = 0.67), surgical groin resection was significantly associated with lower groin recurrence (HR 0.2 (95%CI 0.05-0.92), p = 0.04). The 3-year groin recurrence-free survival (RFS) was significantly higher at 94.4% (87.1-100) in patients with surgical groin resection compared to 79.2% (69.1-90.9) in patients treated with primary radiation (p = 0.02). CONCLUSIONS: In locally advanced squamous cell vulvar cancer, surgical groin management improves groin RFS compared to radiotherapy alone.

Sustainability of an enhanced recovery pathway after minimally invasive gynecologic oncology surgery.

OBJECTIVE: Same day discharge is safe after minimally invasive gynecology oncology surgery. Our quality improvement peri-operative program based on enhanced recovery after surgery principles led to an increase in same day discharge from 30% to 75% over a 12 month period. Twelve months after program implementation, we assessed the sustainability of same day discharge rates, determined post-operative complication rates, and evaluated factors affecting same day discharge rates. METHODS: A retrospective chart review was conducted of 100 consecutive patients who underwent minimally invasive surgery at an academic cancer center from January to 2021 to December 2021. This cohort was compared with the active intervention cohort (n=102) from the implementation period (January 2020 to December 2020). Same day discharge rates and complications were compared. Multivariable analysis was performed to assess which factors remained associated with same day discharge post-intervention. RESULTS: Same day discharge post-intervention was 72% compared with 75% during active intervention (p=0.69). Both cohorts were similar in age (p=0.24) and body mass index (p=0.27), but the post-intervention cohort had longer operative times (p=0.001). There were no significant differences in 30-day complications, readmission, reoperation, or emergency room visits (p>0.05). There was a decrease in 30-day post-operative clinic visits from 18% to 5% in the post-intervention cohort (p=0.007), and unnecessary bowel prep use decreased from 35% to 14% (p<0.001). On multivariable analysis, start time (second case of the day) (OR 0.06; 95% CI 0.01 to 0.35), and ward narcotic use (OR 0.12; 95% CI 0.03 to 0.42) remained associated with overnight admission. CONCLUSION: Same day discharge rate was sustained at 72%, 12 months after the implementation of a quality improvement program to optimize same day discharge rate after minimally invasive surgery, while maintaining low post-operative complications and reducing unplanned clinic visits. To maximize same day discharge, minimally invasive gynecologic oncology surgery should be prioritized as the first case of the day, and post-operative narcotic use should be limited.

Gestational trophoblastic neoplasia: does centralization of care impact clinical management?

OBJECTIVE: International societies advocate for gestational trophoblastic neoplasia referral to designated expert centers. This study assessed the impact of centralization of trophoblastic care on clinical outcomes. METHODS: A centralized program was implemented in 2018 at two affiliated academic hospitals, Princess Margaret Cancer Center and Mount Sinai Hospital. A retrospective analysis of patients treated between 2000 and 2022 was performed and the clinical outcomes were compared before (2000-2017) and after (2018-2022) centralization. Statistical analyses were performed with significance set as p<0.05. RESULTS: A total of 94 patients with trophoblastic neoplasia were included: 60 pre-centralization and 34 post-centralization, 79.8% low-risk and 18.1% high-risk. Centralization led to significant improvement for: (1) accurate score documentation (from 37.9% to 89.3%,); (2) contraception counseling (from 67.2% to 96.7%); (3) median time from diagnosis to chemotherapy (from 9 days to 1 day); and (4) incomplete follow-up (from 20.7% to 3.3%) (all p<0.05). First-line chemotherapy for low-risk neoplasia was dactinomycin in 47.9% and 87.0% pre- and post-centralization, respectively (p=0.005). The median number of chemotherapy cycles decreased from seven to four (p=0.01), and the median number of consolidation cycles increased from two to three (p<0.001). Serum human chorionic gonadotropin (hCG) levels of 10 000-100 000 IU/L were significantly associated with longer time to hCG normalization and higher risk of resistance to first-line chemotherapy compared with hCG levels <1000 IU/L. CONCLUSION: Centralization of trophoblastic neoplasia care leads to greater guideline compliance, faster chemotherapy initiation, fewer chemotherapy cycles with optimized consolidation, and enhanced surveillance completion. This supports the establishment of trophoblastic neoplasia expert centers.

Cost impact analysis of enhanced recovery after minimally invasive gynecologic oncology surgery.

OBJECTIVE: The implementation of a peri-operative care program based on enhanced recovery after surgery principles for minimally invasive gynecologic oncology surgery led to an improvement in same day discharge from 29% to 75% at our center. This study aimed to determine the program's economic impact. METHODS: Our initial enhanced recovery quality improvement program enrolled consecutive patients undergoing minimally invasive hysterectomy at a single center during a 12-month period and compared them to a pre-intervention cohort. The primary outcome was overall costs. The secondary outcomes were surgical and post-operative visit costs. The surgical visit costs included pre-operative and operating room, post-operative stay, pharmacy, and interventions costs. The 30-day post-operative visit costs included clinic and emergency room, and readmission costs. The costs for every visit were collected from the case-cost department and expressed in 2020 Canadian dollars (CAD). RESULTS: A total of 96 and 101 patients were included in the pre- and post-intervention groups, respectively. The median total cost per patient for post-intervention was $7252 compared with $8381 pre-intervention (p=0.02), resulting in a $1129 cost reduction per patient. The total cost for the program implementation was $134 per patient for a total cost of $13 106. The median post-operative stay cost was $816 post-intervention compared with $1278 pre-intervention (p<0.05). Statistically significant savings for the post-intervention group were also found for operative visit, operating room costs, and pharmacy (p<0.05). On multivariate analysis, surgical approach was the only factor associated with operating room costs, whereas both surgical approach and group (pre- vs post-intervention) impacted the total and post-operative stay costs (p<0.05). CONCLUSION: In addition to increasing the same day discharge rate after minimally invasive gynecologic oncology surgery, an enhanced recovery-based peri-operative care program led to significant reductions in cost.

Validation of the Integrated Prediction Model algorithm for outcome of cytoreduction in advanced ovarian cancer.

BACKGROUND: We previously developed the Integrated Prediction Model using a 4-step algorithm of unresectable stage IVB, patient factors, surgical resectability, and surgical complexity to predict outcome of <1 cm cytoreduction in advanced epithelial ovarian cancer, and triaged patients to neoadjuvant chemotherapy or primary cytoreductive surgery. OBJECTIVE: To validate the Integrated Prediction Model on a retrospective cohort of patients. METHODS: A retrospective cohort study of 107 patients with advanced ovarian cancer treated between January 2017 and September 2018 was carried out. The above mentioned 4-step algorithm determined cut-off points using the Youden Index. This validation study reports sensitivity, specificity, negative and positive predictive value on an external cohort. RESULTS: Among 107 patients, 61 had primary surgery and 46 had neoadjuvant chemotherapy. Compared with primary surgery, patients treated with neoadjuvant chemotherapy were significantly older (63.5 vs 61, p=0.037), more likely to have stage IV disease (52% vs 18%, p<0.001), Eastern Cooperative Oncology Group (ECOG) score >1 (30% vs 11%, 0.045), lower pre-operative albumin (37 vs 40, p<0.001), and higher CA-125 (970 vs 227.5, p<0.001). They also had higher patient factors (2 vs 0, p=0.013), surgical resectability (4 vs 1, p<0.001), and anticipated surgical complexity (8 vs 5, p<0.001). There was no significant difference in outcome of cytoreduction (<1 cm residual disease: 85% for primary surgery vs 87% interval surgery, p=0.12)In this validation cohort, triaging patients with patient factors ≤2, surgical resectability score ≤5, and surgical complexity score ≤9 to primary surgery had a sensitivity of 91% for optimal cytoreduction <1 cm and a specificity of 81%. The positive predictive value, negative predictive value, and accuracy were 83%, 90%, and 86%, respectively. Application of the Integrated Prediction Model would have prevented five patients from receiving suboptimal cytoreduction and triaged them to neoadjuvant chemotherapy. CONCLUSIONS: We validated the proposal that a triage algorithm integrating patient factors, surgical complexity, and surgical resectability in advanced ovarian cancer had high sensitivity and specificity to predict optimal cytoreduction <1 cm.

Using a machine learning algorithm to predict outcome of primary cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: To develop a machine learning (ML) algorithm to predict outcome of primary cytoreductive surgery (PCS) in patients with advanced ovarian cancer (AOC) METHODS: This retrospective cohort study included patients with AOC undergoing PCS between January 2017 and February 2021. Using radiologic criteria, patient factors (age, CA-125, performance status, BRCA) and surgical complexity scores, we trained a random forest model to predict the dichotomous outcome of optimal cytoreduction (<1 cm) and no gross residual (RD = 0 mm) using JMP-Pro 15 (SAS). This model is available at https://ipm-ml.ccm.sickkids.ca. RESULTS: One hundred and fifty-one patients underwent PCS and randomly assigned to train (n = 92), validate (n = 30), or test (n = 29) the model. The median age was 58 (27-83). Patients with suboptimal cytoreduction were more likely to have an Eastern Cooperative Oncology Group 3-4 (11% vs. 0.75%, p = 0.004), lower albumin (38 vs. 41, p = 0.02), and higher CA125 (1126 vs. 388, p = 0.012) than patients with optimal cytoreduction (n = 133). There were no significant differences in age, histology, stage, or BRCA status between groups. The bootstrap random forest model had AUCs of 99.8% (training), 89.6%(validation), and 89.0% (test). The top five contributors were CA125, albumin, diaphragmatic disease, age, and ascites. For RD = 0 mm, the AUCs were 94.4%, 52%, and 84%, respectively. CONCLUSION: Our ML algorithm demonstrated high accuracy in predicting optimal cytoreduction in patients with AOC selected for PCS and may assist decision-making.

Integrated prediction model of patient factors, resectability scores and surgical complexity to predict cytoreductive outcome and guide treatment plan in advanced ovarian cancer.

OBJECTIVE: To report performance of an integrated predictive model (IPM) algorithm based on patient factors, surgical resectability and surgical complexity to predict outcome of primary cytoreductive surgery (PCS) and guide treatment plan in patients with advanced epithelial ovarian cancer (AEOC). METHODS: Patients with AEOC between October 2018 and October 2020 were enrolled into a dedicated AEOC program and decision for PCS or neoadjuvant chemotherapy (NACT) was based on multidisciplinary consensus. Data of unresectable stage IVb, patient factors (PF), surgical resectability scores (SRS) and surgical complexity scores (SCS) was prospectively documented. An integrated prediction model (IPM) was developed to predict outcome of optimal (RD < 1 cm) cytoreduction. Retrospective analysis was performed to assess the performance of the IPM. Cut-offs were selected using the Youden Index. RESULTS: Of 185 eligible patients, 81 underwent PCS and 104 were treated with NACT. Patients undergoing PCS had significantly lower median PF (0 vs 2, p < 0.01), SRS (2 vs 4, p < 0.01) and pre-operative SCS (6 vs 8.5, p = 0.01) compared to NACT. In patients undergoing PCS, 88% had optimal cytoreduction and 34.5% had grade 3-4 post-operative complications. A model triaging patients with unresectable Stage IVb, PF > 2, SRS > 5 and SCS > 9 to NACT had 85% sensitivity, 75% specificity and 85% accuracy for outcome of optimal cytoreduction. Our model would have improved triage of 3/10 sub-optimally cytoreduced patients to NACT. For outcome of no-gross residual disease (RD = 0 mm) using the same cut-offs sensitivity and specificity were 85% and 76% respectively. CONCLUSION: The 4-step IPM algorithm had high sensitivity and specificity for optimal cytoreduction with acceptable morbidity without delay to adjuvant therapy. This algorithm may be used to triage patients to PCS or NACT once it is further validated.

First reported case of Robinsoniella peoriensis pyometra and bloodstream infection: A case report and review of the literature.

We report on a 47-year-old woman with jejunal adenocarcinoma and concurrent endometrial cancer, admitted with sepsis. Uterine fluid and blood cultures were positive for Robinsoniella peoriensis. This is the first case report of Robinsoniella peoriensis in Canada. We encourage clinicians to publish their experience treating gynecologic infections caused by Robinsoniella peoriensis. Failure to recognize this pathogen as causative for pyometra, may result in insufficient antimicrobial treatment, and death.

Implementation of a standardized voiding protocol after minimally invasive surgery: A quality improvement initiative.

OBJECTIVES: To assess the effects of the implementation of a standardized voiding protocol in patients undergoing minimally invasive hysterectomy at a single cancer center in terms of the urinary tract infection (UTI) rate, time to first void, and overnight stays secondary to urinary retention. METHODS: We enrolled 102 consecutive patients undergoing minimally invasive hysterectomy at a single cancer center during a 12-month period. A pre-intervention cohort of 100 consecutive patients was identified for comparison. A multidisciplinary team developed and implemented a standardized voiding protocol using quality improvement methodology. We compared the demographics, time to first void, rate of urinary retention, and UTI rates between the pre- and post-intervention cohorts. RESULTS: Our intervention led to a significant reduction in the time to first void (289 min vs. 566 min; P < 0.001), rate of urinary retention (2% vs. 10%; P = 0.015), and postoperative UTI (4% vs. 8%; P = 0.249). There was a similar rate of patients going home with a Foley catheter (9% vs. 11%; P = 0.850). CONCLUSIONS: Implementation of a standardized voiding protocol was associated with a reduction in rate of UTI, time to first void, and overnight stays secondary to urinary retention.

Enhanced recovery after minimally invasive gynecologic oncology surgery to improve same day discharge: a quality improvement project.

OBJECTIVES: Same day discharge after minimally invasive hysterectomy has been shown to be safe and feasible. We designed and implemented a quality improvement perioperative program based on early recovery after surgery principles to improve the rate of same day discharge from 30% to 75% after minimally invasive gynecologic oncology surgery over a 12 month period. METHODS: We enrolled 102 consecutive patients undergoing minimally invasive hysterectomy at a single cancer center during a 12 month period. A pre-intervention cohort of 100 consecutive patients was identified for comparison of clinicodemographic variables and perioperative outcomes. A multidisciplinary team developed a comprehensive perioperative care program and followed quality improvement methodology. Patients were followed up for 30 days after discharge. A statistical process chart was used to monitor the effects of our interventions, and a multivariate analysis was conducted to determine factors associated with same day discharge. RESULTS: Same day discharge rate increased from 29% to 75% after implementation (p<0.001). The post-intervention cohort was significantly younger (59 vs 62 years; p=0.038) and had shorter operative times (180 vs 211 min; p<0.001) but the two groups were similar in body mass index, comorbidity, stage, and intraoperative complications. There was no difference in 30 day perioperative complications, readmissions, reoperations, emergency department visits, or mortality. Overnight admissions were secondary to nausea and vomiting (16%), complications of pre-existing comorbidities (12%), and urinary retention (8%). On multivariate analysis, longer surgery, timing of surgery, and narcotic use on the ward were significantly associated with overnight admission. Overall, 89% of patients rated their experience as 'very good' or 'excellent', and 87% felt that their length of stay was adequate. CONCLUSIONS: Following implementation of a perioperative quality improvement program targeted towards minimally invasive gynecologic oncology surgery, our intervention significantly improved same day discharge rates while maintaining a low 30 day perioperative complication rate and excellent patient experience.

Treatment outcomes and predictive factors in patients ≥70 years old with advanced ovarian cancer.

OBJECTIVE: To evaluate treatment outcomes, survival, and predictive factors in patients ≥70 with advanced epithelial ovarian cancer (AEOC). METHODS: A retrospective single institution cohort study of women ≥70 with Stage III-IV AEOC between 2010 and 2018. Patients had either primary cytoreductive surgery (PCS), neoadjuvant chemotherapy (NACT) with interval cytoreductive surgery (ICS), chemotherapy alone, or no treatment. Demographics, surgical outcome, complications, and survival outcome were compared between groups. RESULTS: Among 248 patients, 69 (27.7%) underwent PCS, 99 (39.9%) had ICS, 56 (22.5%) had chemotherapy alone. Twenty-four (9.6%) remained untreated. Optimal cytoreduction (≤1 cm) was achieved in 72.4% of PCS and 77.8% of NACT/ICS (p = 0.34), without difference in grade ≥3 postoperative complications (15.9% vs. 9.1%, p = 0.37). Progression-free survival (PFS) was 23.5 months in PCS and 15.0 months in ICS patients (hazard ratio [HR]: 1.4, p = 0.041). Patients in the surgical arms, PCS or ICS, had better 2-year overall survival (OS) compared to chemotherapy alone (79%, 68%, 41%, respectively, HR: 3.58, p < 0.001). In a subgroup analysis, patients ≥80 had improved 2-year OS when treated with NACT compared to PCS (82% vs. 57%) and a trend toward improved PFS. Age, stage, and CA-125 were determinants of undergoing PCS. CONCLUSION: In patients ≥70 with AEOC, surgery should not be deferred based on age alone. Fit, well selected patients ≥70 can benefit from PCS, while patients ≥80 might benefit from NACT over PCS.

Efficacy and toxicity of intraperitoneal chemotherapy as compared to intravenous chemotherapy in the treatment of patients with advanced ovarian cancer.

OBJECTIVE: To assess the efficacy and toxicity of intraperitoneal (IP) chemotherapy compared to intravenous (IV) chemotherapy. METHODS: Toxicity profiles, recurrence patterns, and long-term survival outcomes of 271 women with Stage IIIC or IV high-grade serous ovarian cancer (HGSC) treated with primary cytoreductive surgery followed by adjuvant IP or IV chemotherapy during 2001-2015 were reviewed. RESULTS: Women who received IP chemotherapy (n = 91) were more likely to have undergone aggressive and longer surgery with no residual disease compared to the IV arm (n = 180). Chemotherapy-related toxicities were comparable between the two groups. Extraperitoneal recurrences were more common in the IP arm compared to the IV arm. Five-year progression-free survival was 19% versus 18% (P = 0.63) and overall survival was 73% versus 44% (P < 0.01) in the IP versus IV arms, respectively. After adjustment for significant clinicopathologic factors in a multivariable model, use of IP was no longer a statistically significant predictor of overall survival. CONCLUSION: IP chemotherapy in advanced HGSC has not been widely adopted due to concerns about toxicity and inconvenience. Use of IP chemotherapy was associated with comparable safety profile and efficacy to IV chemotherapy in women with Stage IIIC/IV HGSC. Recurrences were more likely to be extraperitoneal with IP treatment.

Implementation of a restrictive opioid prescription protocol after minimally invasive gynecologic oncology surgery.

OBJECTIVES: Opioids are routinely prescribed after minimally invasive gynecologic oncology surgery, with minimal data to inform the ideal dose. The aim of this study was to evaluate the impact of a restrictive opioid prescription protocol on the median morphine milligram equivalents prescribed and pain control in patients undergoing minimally invasive surgery. METHODS: A restrictive opioid prescription protocol was implemented from January through December 2020 at a single tertiary cancer center in Ontario, Canada. Consecutive patients undergoing minimally invasive hysterectomy for suspected malignancy were included. Simultaneously, we implemented use of multimodal analgesia, patient and provider education, pre-printed standardized prescriptions, and tracking of opioid prescriptions. Total median morphine milligram equivalents prescribed were compared between pre- and post-intervention cohorts. Patients were surveyed regarding opioid use and pain control at 30 days post-surgery. RESULTS: A total of 101 women in the post-intervention cohort were compared with 92 consecutive pre-intervention controls. Following protocol implementation, median morphine milligram equivalents prescribed decreased from 50 (range 9-100) to 25 (range 8-75) (p<0.001). In the post-intervention cohort, 75% (76/101) used 10 median morphine milligram equivalents or less and 55 patients (54%) used 0 median morphine milligram equivalent. There was no additional increase in opioid refill requests after implementation of our strategy. Overall, patients reported a median pain score of 3/10 at 30 days post-surgery; the highest pain scores and most of the pain occurred in the first week after surgery. CONCLUSIONS: Implementation of a restrictive opioid prescription protocol led to a significant reduction in opioid use after minimally invasive gynecologic oncology surgery, with over 50% of patients requiring no opioids postoperatively.

Gynecologic oncology treatment modifications or delays in response to the COVID-19 pandemic in a publicly funded versus privately funded North American tertiary cancer center.

OBJECTIVE: To compare gynecologic oncology surgical treatment modifications and delays during the first wave of the COVID-19 pandemic between a publicly funded Canadian versus a privately funded American cancer center. METHODS: This is a retrospective cohort study of all planned gynecologic oncology surgeries at University Health Network (UHN) in Toronto, Canada and Brigham and Women's Hospital (BWH) in Boston, USA, between March 22,020 and July 302,020. Surgical treatment delays and modifications at both centers were compared to standard recommendations. Multivariable logistic regression was performed to adjust for confounders. RESULTS: A total of 450 surgical gynecologic oncology patients were included; 215 at UHN and 235 at BWH. There was a significant difference in median time from decision-to-treat to treatment (23 vs 15 days, p < 0.01) between UHN and BWH and a significant difference in treatment delays (32.56% vs 18.29%; p < 0.01) and modifications (8.37% vs 0.85%; p < 0.01), respectively. On multivariable analysis adjusting for age, race, treatment site and surgical priority status, treatment at UHN was an independent predictor of treatment modification (OR = 9.43,95% CI 1.81-49.05, p < 0.01). Treatment delays were higher at UHN (OR = 1.96,95% CI 1.14-3.36 p = 0.03) and for uterine disease (OR = 2.43, 95% CI 1.11-5.33, p = 0.03). CONCLUSION: During the first wave of COVID-19 pandemic, gynecologic oncology patients treated at a publicly funded Canadian center were 9.43 times more likely to have a surgical treatment modification and 1.96 times more likely to have a surgical delay compared to an equal volume privately funded center in the United States.

The Prevent Ovarian Cancer Program (POCP): Identification of women at risk for ovarian cancer using complementary recruitment approaches.

BACKGROUND: Up to 20% of high-grade serous ovarian carcinomas (HGSOC) are hereditary; however, historical uptake of genetic testing is low. We used a unique combination of approaches to identify women in Ontario, Canada, with a first-degree relative (FDR) who died from HGSOC without prior genetic testing, and offer them multi-gene panel testing. METHODS: From May 2015-Sept 2019, genetic counseling and testing was provided to eligible participants. Two recruitment strategies were employed, including self-identification in response to an outreach campaign and direct targeting of FDRs of deceased HGSOC patients treated at our institution. The rate of pathogenic variants (PV) in established/potential ovarian cancer risk genes and the benefits/challenges of each approach were assessed. RESULTS: A total of 564 women enrolled in response to our outreach campaign (n = 473) or direct recruitment (n = 91). Mean age at consent was 52 years and 96% did not meet provincial testing criteria. Genetic results were provided to 528 individuals from 458 families. The rate of PVs in ovarian cancer risk genes was highest when FDRs were diagnosed with HGSOC <60 years (9.4% vs. 3.9% ≥ 60y, p = 0.0160). Participants in the outreach vs. direct recruitment cohort had a similar rate of PVs; however, uptake of genetic testing (97% vs. 89%; p = 0.0036) and study completion (95% vs. 87%; p = 0.0062) rates were higher in the former. Eleven participants with pathogenic variants have completed risk-reducing gynecologic surgery, with one stage I HGSOC and two breast cancers identified. CONCLUSION: Overall PV rates in this large cohort were lower than expected; however, we provide evidence that genetic testing criteria in Ontario should include individuals with a deceased FDR diagnosed with HGSOC <60 years of age.