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Objective: Determine the cost-effectiveness for hysterectomy versus standard of care single agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN)., Methods: A cost-effectiveness analysis was conducted comparing single agent chemotherapy with hysterectomy using decision analysis and Markov modeling from a healthcare payer perspective in Canada. The base case was a 40-year-old patient with low-risk non-metastatic GTN that completed childbearing. Outcomes were life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and adjusted 2022 costs (CAD). Discounting was 1.5% annually and the time horizon was the patient's lifetime. Model validation included face validity, deterministic sensitivity analyses, and scenario analysis., Results: Mean costs for chemotherapy and hysterectomy arms were $34,507 and $17,363, respectively, while effectiveness measure were 30.37 QALYs and 31.04 LYs versus 30.14 QALYs and 30.82 Lys, respectively. The ICER was $74,526 (USD $54,516) per QALY. Thresholds favoring hysterectomy effectiveness were 30-day hysterectomy mortality below 0.2% and recurrence risk during surveillance above 9.2% (low-risk) and 33.4% (high-risk). Scenario analyses for Dactinomycin and Methotrexate led to similar results. Sensitivity analysis using tornado analysis found the cost to be most influenced by single agent chemotherapy cost and risk of resistance, number of weeks of chemotherapy, and probability of postoperative mortality., Conclusion: Compared to hysterectomy, single agent chemotherapy as a first-line treatment costs $74,526 for each additional QALY gained. Given that this cost falls below the accepted $100,000 willingness-to-pay threshold and waitlist limitations within public healthcare systems, these results support the continued use of chemotherapy as standard of care approach for low-risk GTN., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Timely treatment of epithelial ovarian cancer (EOC) by gynecologic oncologists (GOs) with a combination of surgery and/or chemotherapy has been advocated. Nonetheless, some patients are not assessed by GOs prior to starting their treatment or have surgery by non-GOs. This study aims to determine trends over time in non-mucinous EOC care and to evaluate the impact of care on survival., Methods: Using province-wide administrative data, patients diagnosed with non-mucinous EOC between 2007 and 2018 were identified. Multivariate Cox proportional hazards regression models were used to evaluate the impact of GO assessment prior to initiating treatment or having surgery done by a non-GO on mortality., Results: A total of 10,086 EOC patients were included between 2007 and 2018. During the study period, there was an 8% increase in GO assessment (79% in 2007 to 87% in 2018-19, p ≤  0.001) and a 19% increase in surgeries performed by GOs (69% in 2007 to 88% in 2018-19, p ≤ 0.001). On multivariate analysis, there was an increased hazard of all-cause mortality for patients not assessed by GOs before first treatment (Hazard ratio (HR): 1.61; 95% CI 1.46-1.79). There was an increased hazard of all-cause mortality if ovarian cancer surgery was performed by non-GOs (HR 2.03; 95% CI 1.80-2.30)., Conclusion: Assessment by GO before starting initial treatment is associated with improved survival in women with non-mucinous EOC as the type of surgeon performing primary ovarian cancer surgery. Assessment by GO for all patients with new or suspected ovarian cancer diagnosis before initiation of primary treatment should be advocated., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To determine the 30-day incidence of venous thromboembolism (VTE) after gynecologic oncologic surgery and identify perioperative factors associated with postoperative VTE., Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify all gynecologic oncology cases from 2013 to 2019. Clinical and surgical characteristics, VTE events and 30-day postoperative complications were retrieved. Chi-square analysis and logistic regression models were performed to compare characteristics and postoperative outcomes of patients with and without VTE., Results: A total of 63,198 gynecologic oncology patients were included. The incidence of 30-day postoperative VTE was 1.2% (n = 781). On multivariable analysis, postoperative VTE was significantly associated with ascites (odds ratio (OR) 1.8), disseminated cancer (OR 1.7), pre-operative albumin <30 g/L (OR 1.9), laparotomy (OR 2.8), operative time > 180 min (OR 2.0), and increased surgical complexity (OR 2.2) (all p < 0.001). The incidence of VTE was higher after laparotomy compared to minimally invasive surgery (MIS) (2.3% v. 0.6%, p < 0.001). When stratified by type of gynecologic malignancy undergoing laparotomy, incidence of VTE was higher in patients with ovarian (2.4%) and uterine (2.4%) malignancies, compared to cervical cancer (1.1%) (p < 0.001). The 30-day incidence of VTE was 1.7% in 2013 compared to 0.9% in 2019 (laparotomy: 2.6% in 2013 to 1.6% in 2019 and MIS: 0.8% in 2013 to 0.4% in 2019)., Conclusion: Postoperative VTE is a potentially preventable complication of gynecologic oncology surgery. Our findings indicate that laparotomy, ascites, disseminated cancer, longer operative time, and low pre-operative albumin are risk factors for VTE., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The optimal systemic therapy strategy for advanced epithelial ovarian cancer (EOC) remains unclear. We performed a systematic review and meta-analysis to assess oncologic outcomes and toxicity of bevacizumab combination treatment in advanced EOC., Methods: We conducted an electronic search of all phase 2 and 3 clinical trials involving bevacizumab combination therapy in advanced-stage EOC between 2010 and March 2020, using Embase, Medline, Epub Ahead of Print, Cochrane for clinical trials, Cochrane Database of Systematic Reviews, Web of Science and clinicaltrials.gov databases. Progression-free survival (PFS), overall survival (OS), and their hazard ratios (HR) when available were extracted. Pooled HR were calculated for each efficacy endpoint in the meta-analysis using inverse variance weighted method. Bias was assessed using the Cochrane Collaboration Risk of Bias I (ROB1) tool for randomized controlled trials., Results: Thirty-five studies were included in the qualitative analysis and eight studies in the quantitative synthesis. In the first-line setting, bevacizumab combined with chemotherapy revealed a significant improvement in PFS (pooled HR = 0.72, 95% CI 0.65-0.81) when compared to chemotherapy alone but no significant OS benefit (pooled HR = 0.88, 95% CI 0.72-1.06). In the recurrent setting, bevacizumab combinations showed significant PFS (pooled HR = 0.52, 95% CI 0.47-0.58) and OS benefits (pooled HR = 0.88, 95% CI 0.79-0.99) compared with non-bevacizumab regimens. Rate of bowel perforation was low at 1.24% (range 0-4.2%)., Conclusions: Bevacizumab-containing regimens are associated with significant PFS benefit in advanced and recurrent epithelial ovarian cancer. While the difference in OS did not reach statistical significance in the first-line setting, bevacizumab was associated with improved survival in the recurrent setting., Competing Interests: Declaration of Competing Interest The authors have no personal nor financial conflict of interests to disclose. Several of the clinical trials included in this systematic review were conducted at the Princess Margaret Cancer Centre., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There remains uncertainty about the prognostic significance of residual lung lesion on imaging after completion of treatment of low- or high-risk gestational trophoblastic neoplasia (GTN). Here, we determine if such residual lung lesions are associated with an increased risk of relapse., Methods: We retrospectively screened our electronic database to identify patients with low- or high-risk GTN and lung metastases between 2004 and 18. Recurrences among patients with or without residual lung lesions on imaging were compared. Chi square analysis and Kaplan-Meier survival curves were constructed. As the numbers of cases were low, we combined this data with our previously published and non-overlapping patient cohort (1995-2004)., Results: Of 1304 GTN patients treated at our centre between 2004 and 18, 99 had lung metastases without other distant sites. There were 40 patients (40.4%) with residual lung lesions. Whilst an increased rate of relapse was observed among patients with residual lung lesions (4/40; 10.0%) compared to without such lesions (3/59; 5.1%), this difference was not statistically significant (p = .35). By combining the data with our previous cohort, there was an increase in relapse rate of patients with residual lung lesions (5/63; 7.9%) compared to those without such lesions (4/112; 3.6%). However, this difference was also not statistically significant (p = .21)., Conclusion: Residual lung lesions on imaging after completion of GTN treatment are common. However, this finding did not statistically increase relapse rate. Due to low number of recurrent events, a multi-centre, larger dataset would be needed to provide more definitive evidence., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Real-time intraoperative assessment of anastomotic perfusion with indocyanine green fluorescence angiography (ICG-FA) is a recent technique that is found to assist intraoperative decision-making and decrease risk of anastomotic leak in the General Surgery literature. No studies to date evaluate its use in Gynecologic Oncology. Our objectives were to assess the safety and feasibility of ICG-FA use and to describe the intraoperative assessment of anastomotic perfusion with ICG-FA., Methods: A retrospective study of a prospectively-collected database of patients with a gynecologic malignancy who underwent a bowel resection at Princess Margaret Cancer Centre in Toronto, Canada, between November 1, 2017 and December 15, 2019 was conducted. ICG-FA was administered intravenously, and a near infrared imaging system (Pinpoint, Novadaq, Canada; SPY-PHI, Stryker, USA) was used to objectively assess bowel perfusion., Results: ICG-FA was used to assess a total of 100 bowel anastomoses in 82 consecutive surgeries: 56 low anterior resections, 19 small bowel resections, 15 right hemi-colectomies, 6 left hemi-colectomies, 3 transverse colectomies, and 1 total colectomy. Fifty-five end-to end, 44 side-to-side and 1 end-to-side anastomoses were assessed. ICG angiography was successful in all patients, allowing complete visualization of anastomotic perfusion in all cases. Hypoperfusion detected by ICG-FA resulted in change in operative plan for three patients (two anastomotic revisions and one diverting ileostomy). There were no adverse reactions to ICG. In this cohort, there was one postoperative anastomotic leak., Conclusions: ICG-FA enables objective and accurate intraoperative evaluation of anastomotic perfusion in surgeries for gynecologic malignancies. Its implementation and routine use were found to be safe and well-tolerated without side effects in our study cohort. ICG-FA can be used with other risk-assessment strategies to guide operative decision-making in Gynecologic Oncology., Competing Interests: Declaration of competing interest There are no conflicts of interests to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Heated intraperitoneal chemotherapy (HIPEC) has not been universally adopted at the time of interval cytoreductive surgery for primary epithelial ovarian cancer (EOC) despite evidence of a 12-month overall survival (OS) benefit in a recent landmark randomized trial. We performed a systematic review and meta-analysis to assess oncologic outcomes and perioperative morbidity following HIPEC among primary EOC patients., Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to August 2019, for observational and randomized studies of primary EOC patients undergoing HIPEC. We assessed risk of bias using the Institute of Health Economics Quality Appraisal Checklist for single-arm cohort studies, Newcastle-Ottawa Scale for comparative cohort studies, and Cochrane Collaboration's Tool for randomized trials. We qualitatively summarized survival outcomes and calculated the pooled proportion of 30-day grade III-IV morbidity and postoperative death., Results: We identified 35 articles including 2252 primary EOC patients; one study was a randomized trial, and only six studies included a comparator group of surgery alone. The timing, temperature, and chemotherapeutic agents used for HIPEC differed across studies. Reported OS was highly variable (3-year OS range: 46-77%); three comparative cohort studies and the sole randomized trial reported statistically significant survival benefits for HIPEC over surgery alone, while two comparative cohort studies did not. The pooled proportions for grade III-IV morbidity and postoperative death at 30 days were 34% (95% CI 20-52) and 0% (95% CI 0-5) respectively., Conclusion: One randomized trial suggests that HIPEC at time of interval cytoreductive surgery should be considered in patients with primary EOC. However, there is significant heterogeneity in literature with respect to an appropriate HIPEC regimen, short- and long-term outcomes. High-quality prospective randomized trials are urgently needed to clarify the role of HIPEC in the first-line treatment of primary EOC., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Gynecologic Oncology patients are traditionally admitted for 2-3 days following ileostomy closure. Our aim was to assess feasibility and safety of same-day discharge (SDD), by comparing 30-day clinical outcomes after SDD and standard admission., Methods: Retrospective study of patients who underwent ileostomy closure at two academic tertiary centres in Toronto, Canada, between January 2010 and October 2017., Results: In total 117 patients underwent ileostomy closure: 23 had SDD and 94 were admitted for a median of 3 days. There were no significant differences between groups in terms of age, body mass index, comorbidities, primary malignancy, tumor stage, indication for ileostomy, previous radiation therapy, chemotherapy, interval between ileostomy formation and closure, and intraoperative complications. Median operative time was shorter (47 versus 60 min, p = 0.0001) and there was a longer median interval between last chemotherapy cycle to ileostomy closure (145 versus 106 days, p = 0.01) in the SDD group. SDD was not associated with an increased risk of adverse events (13% versus 24.5%, p= 0.24), as assessed by a composite outcome which included small bowel obstruction, anastomotic leak, surgical site infection, clostridium difficile infection, sepsis, and thromboembolic events, when compared to standard admission. Moreover, SDD did not lead to more emergency room visits (17.4% versus 16%, p = 0.87) or readmissions within 30 days of surgery (17.4% versus 8.5%, p= 0.21)., Conclusions: SDD is a safe alternative to routine hospitalization that has the potential to improve healthcare resource utilization, without increasing readmissions or emergency room visits. Careful patient selection is warranted., Competing Interests: Declaration of competing interest There are no conflicts of interests to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Randomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC., Methods: Retrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan-Meier estimate; the log-rank test was used to compare survival curves., Results: Of the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4 cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs. 1.6%, p=0.033), grade 3 neuropathy (7.8% vs. 0%, p=0.013) and grade 2-3 neutropenia (22.1% vs. 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups., Conclusion: IP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Current recommendations for the use of venous thromboprophylaxis in patients undergoing minimally invasive surgery (MIS) for a gynecologic malignancy are derived from patients undergoing open surgery. Our objective was to determine the 30-day prevalence of symptomatic venous thromboembolism (VTE) after laparoscopic gynecologic oncology procedures in patients who received no thromboprophylaxis., Methods: Between January 2006 and September 2013, women who underwent MIS for endometrial, cervical or ovarian cancer at a single institution were included. Data on patient demographics, diagnosis, comorbidities, perioperative characteristics, use of thromboprophylaxis, and diagnosis of VTE were collected retrospectively., Results: Of the 419 patients who underwent MIS for a gynecologic cancer, 352 (84%) received no VTE prophylaxis. At least a total laparoscopic hysterectomy (simple or radical) or pelvic lymph node dissection was performed in 95% of these patients. The median length of surgery was 137 min and 95% of patients were discharged home within 1 day of surgery. The rate of VTE in the 352 untreated patients was 0.57% (1 pulmonary embolism and 1 deep vein thrombosis). There were no VTE diagnosed within 30 days of surgery in the 67 patients who received anticoagulant thromboprophylaxis., Conclusion: The rate of VTE is low in patients undergoing minimally invasive surgery for a gynecologic malignancy despite no VTE prophylaxis. The benefits of routine use of VTE prophylaxis in this population are questionable., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Non-radical surgery has been proposed in women with early-stage cervical cancer to reduce morbidity. Our objective was to evaluate the outcomes of women with early-stage cervical cancer treated with non-radical surgery., Methods: Between March 1991 and July 2013, 51 women with early-stage cervical cancer underwent simple hysterectomy or cone biopsy. All patients had assessment of pelvic lymph nodes. Patient demographics, stage, perioperative complications, pathology findings and disease-free interval were collected prospectively., Results: Twenty-six women had squamous cell carcinoma (SCC), 22 adenocarcinoma (AC) and 3 adenosquamous (AS) carcinoma. Thirty women were FIGO stage 1A1, 8 women IA2, and 13 women 1B1. Twenty-two (43%) and 29 (57%) women underwent simple hysterectomy and cone biopsy respectively. Median measurable tumor size was 10mm (range 2-11), and median depth of invasion was 2.0mm (range 0.1-12 mm). Lymphovascular space invasion (LVSI) was present in 18 women (35%). Surgical margins were negative in all women. Two women received adjuvant chemoradiation (one had deep stromal invasion with LVSI, and one had two micrometastases to pelvic nodes). Forty-nine women (96%) had their Foley catheter removed on the day of surgery or post-operative day 1. No intraoperative or postoperative complications occurred and the median blood loss was 100ml. Median follow-up was 21 months (range 1-112). None of the 51 women developed a recurrence during follow-up (95% CI: 0-6%)., Conclusion: Non-radical surgery in appropriately selected early-stage cervical cancer patients results in a low complication rate and excellent oncologic outcomes. This approach seems to be a reasonable option in well-selected patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To compare the relative value of two methods of detection for the sentinel lymphatic nodes (SLNs): colorimetric with Isosulfan blue (ISB) and radio-isotopic with Technetium-99 (Tc99), and to evaluate the concept of the SLN mapping applied to cervical cancer., Methods: From October 2000 to December 2006, radical surgery was planned in 211 patients who presented early-stage cancer of the cervix. Both ISB and Tc99 were used to detect the SLNs. In all cases, we proceeded with laparoscopy for the identification and removal of the SLNs, followed by a complete pelvic lymphadenectomy with or without para-aortic node sampling. The SLNs were sent for frozen section (1 level) and were ultra-staged (6 levels) for final pathology. Detection rate, sensitivity and negative predictive value (NPV) were calculated., Results: Among the 211 patients, ISB (n=152) identified at least 1 SLN in 92.8% of the cases. With Tc99 (n=166), the detection rate of SLN increased to 96.9%. When both techniques were used together (n=107), Tc99 was significantly better than ISB by 7.8% (p=0.0094) and at least 1 SLN (hot and/or blue) was found in 99.1% of the cases. In 16.7% of patients, a SLN was located in aberrant sites, including 3.8% in the para-aortic area. Thirty-three out of the 211 patients (15.6%) had lymph node metastases. When considering only the 181 patients with bilateral SLNs identified, the NPV of SLN is 100% after ultra staging on final pathology and 94.2% on frozen section (FS)., Conclusion: Sentinel node mapping is feasible using laparoscopy. The radio-isotopic technique adds significantly to the rate of detection. The main benefits of SLN mapping in cervical cancer are the detection of micro-metastases on ultra staging which might be missed on routine pathological evaluation, and identification of aberrant drainage sites. However, the current frozen section techniques lack sensitivity to identify very small metastases and need refinement. SLN mapping should become the standard of care in the modern management of cervical cancer and complete pelvic lymphadenectomy could be avoided when bilateral SLNs are detected in patients with lesions less than 2 cm., (Copyright © 2011 Elsevier Inc. All rights reserved.)