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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.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.Our ML algorithm demonstrated high accuracy in predicting optimal cytoreduction in patients with AOC selected for PCS and may assist decision-making.

ObjectiveTo evaluate oncologic outcomes in patients with stage I endometrioid ovarian cancer treated with fertility-sparing compared with conventional surgery and to describe reproductive outcomes.MethodsA retrospective cohort study was carried out of patients aged 18–45 with stage I, grade 1 and 2 (low-grade) endometrioid ovarian cancer treated at two cancer centers between July 2001 and December 2019. Clinical and pathologic characteristics were compared using Fisher’s exact test for categorical and the Mann–Whitney U test for continuous variables. Recurrence-free and overall survival were calculated from Kaplan–Meier curves and compared for fertility-sparing and conventional surgery using the log rank test. Pregnancy outcomes are described.ResultsThere were 230 patients with endometrioid ovarian cancer. After exclusion of patients with stage greater than I and those older than 45 years, there were 31 patients with stage I cancer aged 18–45. Of these patients, 11 (35.5%) underwent fertility-sparing surgery and 20 (64.5%) underwent conventional surgery. The median follow-up was 6.0 years (range 1.8–17.3). The median age was 36 years (range 26–42) in the fertility-sparing group and 42 years (range 35–45) in the conventional surgery group (p=0.001), with no difference in other clinical and pathologic characteristics. The 5-year recurrence-free survival was 90.9% (95% CI 73.9% to 100%) for the fertility-sparing group and 84.0% (95% CI 67.3% to 100%) for the conventional surgery group (p=0.65). The 5-year overall survival was 100% for patients in the fertility-sparing group and 92.6% (95% CI 78.7% to 100%) for patients treated with conventional surgery (p=0.49). Four (12.9%) patients had disease recurrence: three (15%) after conventional surgery and one (9.1%) in the contralateral ovary after fertility-sparing surgery and embryo cryopreservation. After fertility-sparing surgery, seven (63.6%) patients attempted pregnancy, of which five (71.4%) conceived with four (57.1%) usingin vitrofertilization. Of the five patients who conceived, there were three spontaneous abortions and five live births.ConclusionFertility-sparing surgery appears safe and may be considered in young women with stage I, low-grade endometrioid ovarian cancer when fertility preservation is desired.

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.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.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).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.

ObjectivesSame 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.MethodsWe 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.ResultsSame day discharge rate increased from 29% to 75% after implementation (pConclusionsFollowing 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.

To evaluate treatment outcomes, survival, and predictive factors in patients ≥70 with advanced epithelial ovarian cancer (AEOC).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.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.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.

ObjectiveThe preoperative neutrophil-to-lymphocyte ratio has been found to be an independent prognostic indicator for perioperative complications and survival outcomes in patients undergoing oncologic surgery for several malignancies. The objective of this study was to evaluate the role of the preoperative neutrophil-to-lymphocyte ratio in predicting 30-day postoperative morbidity and overall survival in advanced-stage high-grade serous ovarian cancer patients after primary surgery.MethodsA retrospective study was conducted on consecutive patients who underwent primary surgery for high-grade serous ovarian cancer between January 2008 and December 2016 at a single tertiary academic institution in Toronto, Canada. Optimal thresholds for preoperative neutrophil-to-lymphocyte ratio were determined using receiver-operator characteristic curve analysis. Cox-proportional hazard models, Kaplan-Meier, and logistic regression analyses were performed.ResultsOf 505 patients with ovarian cancer during the study period, 199 met the inclusion criteria. Receiver-operator characteristic curve analysis generated optimal preoperative neutrophil-to-lymphocyte ratio thresholds of 2.3 and 2.9 for 30-day postoperative morbidity and survival outcomes, respectively. A neutrophil-to-lymphocyte ratio ≥2.3 was predictive of a composite outcome of 30-day postoperative complications (odds ratio 7.3, 95% confidence interval 2.44 to 21.81; p=0.0004), after adjusting for longer operative time and intraoperative complications. Postoperative complications included superficial surgical site infections (p=0.007) and urinary tract infections (p=0.004). A neutrophil-to-lymphocyte ratio ≥29 was associated with worse 5-year overall survival (57.8% vs 77.7%, p=0.003), and suggested no statistically significant difference in progression-free survival (33.8% vs 40.7%, p=0.054). On multivariable analysis, the neutrophil-to-lymphocyte ratio remained an independent predictor for overall survival (p=0.02) when adjusting for suboptimal cytoreduction (p≤0.0001).DiscussionA preoperative neutrophil-to-lymphocyte ratio ≥2.3 and ≥2.9 is associated with greater risk of 30-day postoperative morbidity and worse overall survival, respectively. This marker may be used in conjunction with other risk assessment strategies to preoperatively identify high-risk patients. Further prospective study is required to investigate its role in clinical decision-making.

ObjectivesTo assess the effect of complete surgical staging and adjuvant chemotherapy on survival in stage I, low grade endometrioid ovarian cancer.MethodsThis retrospective study was conducted at two cancer centers from July 2001 to December 2019. Inclusion criteria were all stage I, grade 1 and 2 endometrioid ovarian cancer patients. Patients with mixed histology, concurrent endometrial cancer, neoadjuvant chemotherapy, and patients who did not undergo follow-up at our centers were excluded. Clinical, pathologic, recurrence, and follow-up data were collected. Cox proportional hazard model evaluated predictive factors. Recurrence-free survival and overall survival were calculated using the Kaplan-Meier method.ResultsThere were 131 eligible stage I patients: 83 patients (63.4%) were stage IA, 5 (3.8%) were stage IB, and 43 (32.8%) were stage IC, with 80 patients (61.1%) having grade 1 and 51 (38.9%) patients having grade 2 disease. Complete lymphadenectomy was performed in 34 patients (26.0%), whereas 97 patients (74.0%) had either partial (n=22, 16.8%) or no (n=75, 57.2%) lymphadenectomy. Thirty patients (22.9%) received adjuvant chemotherapy. Median follow-up was 51.5 (95% CI 44.3 to 57.2) months. Five-year recurrence-free survival was 88.0% (95% CI 81.6% to 94.9%) and 5 year overall survival was 95.1% (95% CI 90.5% to 99.9%). In a multivariable analysis, only grade 2 histology had a significantly higher recurrence rate (HR 3.42, 95% CI 1.03 to 11.38; p=0.04). There was no difference in recurrence-free survival (p=0.57) and overall survival (p=0.30) in patients with complete lymphadenectomy. In stage IA/IB, grade 2 there was no benefit of adjuvant chemotherapy (p=0.19), and in stage IA/IB, low grade without complete surgical staging there was no benefit of adjuvant chemotherapy (p=0.16). Twelve patients (9.2%) had recurrence; 3 (25%) were salvageable at recurrence and are alive with no disease.ConclusionsPatients with stage I, low grade endometrioid ovarian cancer have a favorable prognosis, and adjuvant chemotherapy and staging lymphadenectomy did not improve survival.

ObjectivesOpioids 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.MethodsA 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.ResultsA 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) (pConclusionsImplementation 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.

High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.

BackgroundPatients with recurrent clear cell ovarian cancer have poor prognosis and limited effective systemic treatment options.ObjectivesTo characterize patterns of recurrence and compare overall survival and post-recurrence survival parameters in patients with recurrent ovarian clear cell carcinoma.MethodsClinical data on patients with ovarian clear cell carcinoma between June 1995 and August 2014 were collected. Patients with clear cell ovarian cancer recurrence were included in this study. Patients with different histologic sub-type, persistent or progressive disease on completion of the initial treatment were excluded. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to quantify survival differences on univariable analysis. To search for significant covariates related to the overall survival and post-recurrence survival, a univariable Cox proportional hazard model was performed.ResultsA total of 209 patients met inclusion criteria. Of these, 61 (29%) patients who were free of disease at completion of the initial treatment had recurrence. Patterns of recurrence were as follows: 38 (62%) patients had multiple-site recurrence, 12 (20%) had single-site recurrence, and 11 (18%) had nodal recurrence only. The median overall survival was 44.7 months (95% CI 33.4 to 64.2) and was significantly associated with pattern of recurrence (p=0.005). The median post-recurrence survival was 18.4 months (95% CI 12.5 to 26.7): 54.4 months (95% CI 11 to 125.5) in single-site recurrence, 13.7 months (95% CI 6.8 to 16.5) in multiple-site recurrence, and 30.1 (95% CI 7.2 to 89) months in nodal recurrence (p=0.0002). In the multivariable analysis, pattern of recurrence was a predictor of post-recurrence survival.Six patients (9.8%) had a prolonged disease-free interval after recurrence (disease-free for more than 30 months after completion of treatment for recurrence). Prolonged recurrences were noted in 4 (33%) of 12 patients with single-site recurrence, 1 (9%) of 11 patients with nodal recurrence, and in 1 (2.7%) of 38 patients with multiple-site recurrence. Three of the six patients with a prolonged disease-free interval after recurrence were treated surgically at the time of recurrence.ConclusionOvarian clear cell carcinoma predominantly recurs in multiple sites and it is associated with a high mortality rate and short post-recurrence survival. When recurrences are limited to a single site, or only to lymph nodes, the median post-recurrence survival is longer. Disease-free interval after recurrence is longer in patients with single-site recurrence who are treated surgically at the time of recurrence.

5546 Background: In advanced ovarian cancer, the decision for primary cytoreductive surgery(PCS) or neoadjuvant chemotherapy(NACT) remains a challenge and may impact survival. We previously developed the integrated prediction model(IPM) using a 4-step algorithm of unresectable stage IVb, patient factors, surgical resectability and surgical complexity to predict outcome of optimal cytoreduction in advanced epithelial ovarian cancer(AEOC) and triage patients to NACT or PCS. The objective of the current study was to validate this model on a retrospective historical cohort of patients. Methods: This is a retrospective cohort study of 107 patients with AEOC treated at the Princess Margaret Cancer Centre between January 2017 and September 2018 undergoing PCS or NACT. All diagnostic imaging was retrospectively reviewed to assign surgical resectability score (SRS) for sites of disease and the surgical complexity score (SCS) for procedures anticipated to be required to achieve optimal cytoreduction based on pre-operative imaging. Those scores were modified from previously validated tools. Patient factors (PF) included age, ECOG and albumin. We previously developed an IPM algorithm to achieve outcome of optimal cytoreduction and determined cut-offs using the Youden index J. Triaging patients to PCS without stage IVb unresectable disease, PF≤ 2, SRS≤5 and SCS≤ 9 led to an 85% specificity and 75% accuracy for outcome of optimal cytoreduction < 1 cm. The current validation study was performed reporting sensitivity, specificity, negative (NPV) and positive predictive value (PPV) on an external cohort. Results: Among 107 patients, 61 had PCS and 46 had NACT followed by ICS. Patients treated with NACT were significantly older (63.5 vs 61 years, p = 0.037), more likely stage IV (52% vs 18%, p < 0.001), had a higher proportion of ECOG > 1 (30% vs 11%, 0.045), a lower pre-operative album (37 vs 40, p < 0.001) and higher CA-125 (970 vs 227.5, p < 0.001) compared to PCS. They also had higher PF (2 vs 0, p = 0.013), SRS (4 vs 1, p < 0.001) and SCS (8 vs 5, p = < 0.001). There was no significant difference in outcome of cytoreduction; the optimal cytoreduction rate was 85% vs 87%, p = 0.12 between PCS and ICS patients. In this validation cohort, triaging patients without unresectable stage IVb disease, PF≤ 2, SRS≤ 5 and SCS≤ 9 to PCS had a sensitivity of 91% to correctly identify patients who will have optimal cytoreduction of < 1 cm at PCS and a specificity of 81%. The PPV was 83%, NPV was 90% and accuracy was 86%. Application of the IPM would have prevented 5 suboptimal patients and correctly triaged them to NACT. Conclusions: We validated a triage algorithm integrating patient factors, surgical complexity and surgical resectability for patients with AEOC to achieve optimal cytoreduction at PCS with high sensitivity and specificity. This may therefore be used in a clinical setting to decide between PCS and NACT.

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.

ObjectiveMucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer with scarce literature guiding its management. We aimed to investigate the optimal surgical management of clinical stage I mucinous ovarian carcinoma by examining the prognostic significance of lymphadenectomy and intra-operative rupture on patient survival.MethodsWe conducted a retrospective cohort study of all pathology-reviewed invasive mucinous ovarian carcinomas diagnosed between 1999 and 2019 at two tertiary care cancer centers. Baseline demographics, surgical management details, and outcomes were collected. Five-year overall survival, recurrence-free survival, and the association of lymphadenectomy and intra-operative rupture on survival were examined.ResultsOf 170 women with mucinous ovarian carcinoma, 149 (88%) had clinical stage I disease. Forty-eight (32%; n=149) patients had a pelvic and/or para-aortic lymphadenectomy, but only 1 patient with grade 2 disease was upstaged due to positive pelvic lymph nodes. Intra-operative tumor rupture was documented in 52 cases (35%). On multivariable analysis, after adjusting for age, final stage, and use of adjuvant chemotherapy, there was no significant association between intra-operative rupture with overall survival (HR 2.2 (0.6–8.0); p=0.3) or recurrence-free survival (HR 1.3 (0.5–3.3); p=0.6), or lymphadenectomy with overall survival (HR 0.9 (0.3–2.8); p=0.9) or recurrence-free survival (HR 1.2 (0.5–3.0); p=0.7). Advanced stage was the only factor that was significantly associated with survival.ConclusionsIn clinical stage I mucinous ovarian carcinoma, systematic lymphadenectomy has low utility, as very few patients are upstaged and recurrence typically occurs in the peritoneum. Furthermore, intra-operative rupture does not appear to independently confer a worse survival, and therefore these women may not benefit from adjuvant treatment based on rupture alone.

Objectives: The rate of perioperative adverse events, postoperative outcomes and survival between patients aged 60-69 yo versus those ≥70 yo undergoing surgery for the primary treatment of advanced ovarian cancer (OC). Methods: We retrospectively identified all patients ≥60 years old treated surgically for primary advanced high-grade OC at our institution between January 2016 and December 2018. Institutional National Surgical Quality Improvement Program data were obtained for post-operative complications. Additional data were abstracted from medical records. Results are stratified based on the treatment approach: primary debulking surgery (PDS) or neo-adjuvant chemotherapy followed by interval debulking surgery (NACT/IDS). Appropriate statistical tests were performed. Results: A total of 77 patients were analyzed; 45 were between 60-69 years and 32 were ≥70 years. There were no differences in preoperative BMI, ECOG, ASA, CCI, polypharmacy, baseline bloodwork and stage (Table 1). Only 2 patients ≥70 years (0.6%) saw a geriatric oncology specialist prior to treatment. A total of 32 patients underwent PDS (60-69yo: n=18, ≥70yo: n=14), and 45 patients had NACT/IDS (60-69yo: n=27, ≥70yo: n=18). In both PDS and NACT/IDS groups, there were no differences in the post-operative adverse events between the two age groups. Older patients in the NACT/IDS group received less total platinum and taxane chemotherapy before and after surgery compared to NACT/IDS patients aged 60-69 years (p Download : Download high-res image (144KB) Download : Download full-size image Download : Download high-res image (263KB) Download : Download full-size image Conclusions: Although baseline characteristics were comparable between younger and older OC patients, reasons for PDS versus NACT/IDS were difficult to extrapolate from the medical record. Age was not a factor influencing perioperative outcomes of advanced ovarian cancer patients and the main predictor of outcomes was treatment approach. Since PDS is the main predictor of survival, a standardized, multi-disciplinary approach to optimize the management of older patients with ovarian cancer is necessary. Use of a formal assessment tool and consultation with a geriatric specialist may facilitate more patients undergoing PDS.

Objectives: Mucinous ovarian carcinoma (MOC) is the most common histology in young women eligible for fertility-sparing surgery. The aim of the study was to evaluate the safety and reproductive outcomes after fertility-sparing surgery in invasive mucinous ovarian carcinomas. Methods: A retrospective review was performed of all MOCs diagnosed between 1999 and 2019 at two tertiary care cancer centers. Pathology was reviewed to rule out cases with metastasis from gastrointestinal tract primary. The demographics and survival outcomes were compared between women who underwent fertility-sparing surgery and those who underwent radical surgery (at least hysterectomy, bilateral salpingo-oophorectomy±staging). Five-year overall survival (OS) and recurrence free survival (RFS) were calculated from Kaplan-Meier curves and comparisons made using log-rank test. Cox proportional hazard models were constructed to evaluate the effect of fertility sparing surgery on survival. Results: Of 149 women with apparent stage I disease upon presentation, 43 (29%) underwent fertility-sparing surgery in the form of unilateral salpingo-oophorectomy±omentectomy and lymphadenectomy. Compared to women who underwent radical surgery, these women were younger (30 years vs 55 years; p Conclusions: Fertility-sparing surgery in apparent stage I MOC is not associated with worse survival outcomes; however, it is important that candidates are carefully selected based on pathologic factors. In those with aggressive histologic components, radical surgery should be considered.

Background It is unclear whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy in women with high grade endometrial cancer (EC). We performed a prospective multicenter cohort study (the SENTOR trial) to evaluate the diagnostic accuracy of SLNB using indocyanine green in intermediate and high grade EC (NCT01886066). Methods Patients with clinical stage I grade 2 endometrioid or high grade EC scheduled for minimally invasive hysterectomy at three academic centers in Toronto, Canada, were prospectively enrolled for SLNB followed by pelvic (PLND) and para-aortic lymphadenectomy (PALND) as the reference standard. The study was powered to determine sensitivity of the SLNB algorithm as the primary endpoint. Results We enrolled 156 patients (126 high grade); all underwent SLNB and PLND, and 106 (84%) with high grade EC underwent PALND. Sentinel lymph node detection rates were 97% per patient (95% CI 94–99), 88% per hemipelvis (95% CI 83–91), and 78% bilaterally (95% CI 70–84). Of 27 patients (17%) with nodal metastases, 26 were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI 81–100), false negative rate of 4% (95% CI 0–19), and negative predictive value of 99% (95% CI 96–100). Only one patient (0.6%) was misclassified by the SLNB algorithm. Two of 27 node-positive patients (7.5%) were identified outside traditional PLND boundaries, and five of 27 (18.5%) required immunohistochemistry for diagnosis. Conclusion SLNB has comparable, if not superior, diagnostic accuracy relative to lymphadenectomy in high grade EC patients. SLNB is a viable option for the surgical staging of EC.

Key Points Question What is the diagnostic accuracy of sentinel lymph node biopsy (SLNB) compared with lymphadenectomy in women with intermediate- and high-grade endometrial cancer? Findings In this cohort study of 156 patients with endometrial cancer (126 with high-grade histologic subtypes), SLNB had a sensitivity of 96% and a negative predictive value of 99% for the detection of nodal metastasis. A total of 26% of patients with node-positive cancer were identified outside lymphadenectomy boundaries or required immunohistochemistry for diagnosis. Meaning In this study, SLNB had similar diagnostic accuracy and prognostic ability as lymphadenectomy in patients with high-grade endometrial cancer at greatest risk for nodal metastasis., Importance Whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear. Objective To examine the diagnostic accuracy of, performance characteristics of, and morbidity associated with SLNB using indocyanine green in patients with intermediate- and high-grade EC. Design, Setting, and Participants In this prospective, multicenter cohort study (Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging [SENTOR] study), accrual occurred from July 1, 2015, to June 30, 2019, with early stoppage because of prespecified accuracy criteria. The study included patients with clinical stage I grade 2 endometrioid or high-grade EC scheduled to undergo laparoscopic or robotic hysterectomy with an intent to complete staging at 3 designated cancer centers in Toronto, Ontario, Canada. Exposures All patients underwent SLNB followed by lymphadenectomy as the reference standard. Patients with grade 2 endometrioid EC underwent pelvic lymphadenectomy (PLND) alone, and patients with high-grade EC underwent PLND and para-aortic lymphadenectomy (PALND). Main Outcomes and Measures The primary outcome was sensitivity of the SLNB algorithm. Secondary outcomes were additional measures of diagnostic accuracy, sentinel lymph node detection rates, and adverse events. Results The study enrolled 156 patients (median age, 65.5 years; range, 40-86 years; median body mass index [calculated as weight in kilograms divided by height in meters squared], 27.5; range, 17.6-49.3), including 126 with high-grade EC. All patients underwent SLNB and PLND, and 101 patients (80%) with high-grade EC also underwent PALND. Sentinel lymph node detection rates were 97.4% per patient (95% CI, 93.6%-99.3%), 87.5% per hemipelvis (95% CI, 83.3%-91.0%), and 77.6% bilaterally (95% CI, 70.2%-83.8%). Of 27 patients (17%) with nodal metastases, 26 patients were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI, 81%-100%), a false-negative rate of 4% (95% CI, 0%-19%), and a negative predictive value of 99% (95% CI, 96%-100%). Only 1 patient (0.6%) was misclassified by the SLNB algorithm. Seven of 27 patients with node-positive cancer (26%) were identified outside traditional PLND boundaries or required immunohistochemistry for diagnosis. Conclusions and Relevance In this prospective cohort study, SLNB had acceptable diagnostic accuracy for patients with high-grade EC at increased risk of nodal metastases and improved the detection of node-positive cases compared with lymphadenectomy. The findings suggest that SLNB is a viable option for the surgical staging of EC., This cohort study examines the diagnostic accuracy, performance characteristics, and morbidity associated with sentinel lymph node biopsy in patients with intermediate- and high-grade endometrial cancer.

ObjectiveOvarian clear cell carcinoma has unique clinical and molecular features compared with other epithelial ovarian cancer histologies. Our objective was to describe the incidence of second primary malignancy in patients with ovarian clear cell carcinoma.MethodsRetrospective cohort study of patients with ovarian clear cell carcinoma at two tertiary academic centers in Toronto, Canada between May 1995 and June 2017. Demographic, histopathologic, treatment, and survival details were obtained from chart review and a provincial cancer registry. We excluded patients with histologies other than pure ovarian clear cell carcinoma (such as mixed clear cell histology), and those who did not have their post-operative follow-up at these institutions.ResultsOf 209 patients with ovarian clear cell carcinoma, 54 patients developed a second primary malignancy (25.8%), of whom six developed two second primary malignancies. Second primary malignancies included: breast (13), skin (9), gastrointestinal tract (9), other gynecologic malignancies (8), thyroid (6), lymphoma (3), head and neck (4), urologic (4), and lung (4). Eighteen second primary malignancies occurred before the index ovarian clear cell carcinoma, 35 after ovarian clear cell carcinoma, and 7 were diagnosed concurrently. Two patients with second primary malignancies were diagnosed with Lynch syndrome. Smoking and radiation therapy were associated with an increased risk of second primary malignancy on multivariable analysis (OR 3.69, 95% CI 1.54 to 9.07, p=0.004; OR 4.39, 95% CI 1.88 to 10.6, p=0.0008, respectively). However, for patients developing second primary malignancies after ovarian clear cell carcinoma, radiation therapy was not found to be a significant risk factor (p=0.17). There was no significant difference in progression-free survival (p=0.85) or overall survival (p=0.38) between those with second primary malignancy and those without.ConclusionPatients with ovarian clear cell carcinoma are at increased risk of second primary malignancies, most frequently non-Lynch related. A subset of patients with ovarian clear cell carcinoma may harbor mutations rendering them susceptible to second primary malignancies. Our results may have implications for counseling and consideration for second primary malignancy screening.

ObjectivesMinimally invasive radical hysterectomy is associated with decreased survival in patients with early cervical cancer. The objective of this study was to determine whether the use of an intra-uterine manipulator at the time of laparoscopic or robotic radical hysterectomy is associated with inferior oncologic outcomes.MethodsA retrospective cohort study was carried out of all patients with cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) International Federation of Gynecology and Obstetrics 2009 stages IA1 (with positive lymphovascular space invasion) to IIA who underwent minimally invasive radical hysterectomy at two academic centers between January 2007 and December 2017. Treatment, tumor characteristics, and survival data were retrieved from hospital records.ResultsA total of 224 patients were identified at the two centers; 115 had surgery with the use of an intra-uterine manipulator while 109 did not; 53 were robotic and 171 were laparoscopic. Median age was 44 years (range 38–54) and median body mass index was 25.8 kg/m2 (range 16.6–51.5). Patients in whom an intra-uterine manipulator was not used at the time of minimally invasive radical hysterectomy were more likely to have residual disease at hysterectomy (pConclusionAfter controlling for adverse pathological factors, the use of an intra-uterine manipulator in patients with early cervical cancer who underwent minimally invasive radical hysterectomy was not an independent factor associated with rate of recurrence.

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.

Objectives: Urinary retention after pelvic surgery is common and contributes to postoperative catheter-associated urinary tract infection (UTI). The aim of our quality improvement study was to reduce the rate of UTI by 50% during the study period. Methods: A standardized voiding protocol was designed and implemented in patients undergoing minimally invasive hysterectomy for gynecologic malignancy between January to September 2020. The protocol included: 1) aseptic indwelling catheter insertion technique, 2) use of a new catheter for every insertion attempt, 3) proper positioning of the catheter bag below the patient's bladder on the side of the table during surgery, 4) catheter removal immediately after surgery prior to transfer to recovery room, 5) bladder scan after void, 6) and limiting repeat catheterizations for retention (Figure 1). We compared the demographics, time to first void, rate of urinary retention, and UTI rates between the pre- and post-protocol cohorts. Data for the historical cohort was obtained using the National Surgical Quality Improvement Program (NSQIP) database. Chi-square and Fisher's exact tests were used for comparison of categorical variables and Wilcoxon Rank-Sum tests for continuous variables. Results: A total of 79 post-protocol patients were compared to 124 patients in a historical cohort. The post-implementation cohort was younger (59 vs 65; p=0.04) but clinical and surgical characteristics were not statistically different between the two cohorts. The voiding protocol led to a significant decrease in the interval to first void (289 vs 526 minutes; p Conclusions: Implementation of a standardized voiding protocol was associated with a significant reduction in time to first void, and 50% decreased catheter-associated UTI.

Objectives: The major shift in health-care resource utilization during the COVID-19 pandemic to support patients requiring mechanical ventilation and intensive care monitoring has led to unprecedented cancellations of elective surgeries and reductions of ambulatory clinic visits worldwide. The primary objective of this study is to determine whether the response to the pandemic resulted in modifications, cancellations or delays to the standard therapeutic algorithms for patients with gynecologic malignancies at tertiary, large-volume publicly funded Canadian cancer centers as compared to a privately funded American cancer center. Methods: This is a retrospective cohort study of all surgical oncology and gynecologic oncology cases performed in the province of Ontario and at the University Health Network/Princess Margaret Cancer Center (UHN/PMH) as a surrogate for treatment delays, compared to all gynecologic oncology patients treated at the Dana Farber Cancer Institute, Boston, MA, USA, between March 3, 2020-June 30, 2020. Descriptive statistics and treatment times were analysed using SPSS 25.0 Results: In the province of Ontario, between March 15, 2020-October 25, 2020, there was a 19% overall decrease in surgical oncology volumes compared to the same time period the previous year (March 17, 2019-Oct 17, 2019). There was an increase of 96% in high priority surgical oncology cases and a 43% decrease in low priority cancer cases. Surgeries for gynecologic malignancies decreased by 8% in the province of Ontario as compared to the previous year. At UHN/PMH, a publicly funded tertiary cancer center in Ontario, there was a 59.8% reduction in surgical oncology volumes between March 09, 2020-May 04 2020, as compared to the previous year (March 04, 2019-April 29 2019). In comparison, at the Dana Farber Cancer Institute, a privately funded tertiary cancer center, there were 202 new gynecologic oncology patient referrals and 66 returning patients between March 3, 2020-June 30, 2020. The median time from referral to first consultation for new patients was 11 days (range 1-21) and the time to primary treatment was 31 days (range 5-157). New patients with ovarian malignancies had the shortest time to treatment of 22 days (range 5-157). There were no modifications made to the standard of care treatment plans for any patients and 5.7% of the patients had treatment delays. Conclusions: During the COVID-19 pandemic, the public Canadian healthcare system in the province of Ontario was subjected to a 19% reduction in surgical oncology volumes and 8% specifically for gynecologic oncology surgeries, while there was a 5.7% treatment delay for gynecologic oncology surgeries for a similar patient cohort treated at a tertiary cancer center in a privately funded health care system in the United States.

Objectives: To determine the effect of lymphadenectomy and adjuvant chemotherapy on survival in stage I, grade 1 (G1) and 2 (G2) endometrioid ovarian cancer (EnOC) as there is limited evidence in this population. Methods: Retrospective cohort study of patients with stage I, G1 and G2 EnOC, treated at two cancer centers between 2001-2019. Demographic, surgical and follow up data was collected. Recurrence free survival (RFS) and overall survival (OS) were calculated from the Kaplan-Meier curves. Cox Proportional Hazard was used to evaluate predictive factors. Results: There were 192 G1 and G2 EnOC, 129 had stage I disease upon presentation. Twenty-nine patients were upstaged after surgery: 25 patients were stage II and 4 patients were stage III based on omental or bowel involvement. Nine patients had CT findings concerning for advanced stage, but were found to be stage I following surgery. In total, there were 131 patients with stage I disease. The median age for the stage I patients (n=131) was 54 (26-90) years, 80 patients had G1 and 51 had G2 disease, 84 patients were stage IA, 5 were IB and 42 were stage IC. Complete staging lymphadenectomy was performed in 34/131 (26.0%) whereas 97 had either partial (n=22) or no (n=75) surgical staging. Adjuvant chemotherapy was given in 30 patients. Median (95% CI) follow-up was 51.5 months (44.3-57.2). Median RFS was 48.2 (42.3-54.0) months and median OS time was 51.5 (44.3-57.2) months. In the univariate analysis, including age, complete staging, and chemotherapy, only grade was found to be significant with G2 more likely recurrence, compared to G1 patients (p=0.03). This was further validated in the multivariable analysis (p=0.04; HR=3.42 95% CI 1.03-11.38). There was no difference in RFS (p=0.57) and OS (p=0.30) in patients who underwent complete surgical staging compared to those that did not. None of the 56 patients that had complete (n=34) or partial (n=22) lymphadenectomy had positive lymph nodes. For a subgroup of 70 patients with stage IA/IB that did not have complete surgical staging, adjuvant chemotherapy was given to 10 patients. Sixty patients had no adjuvant treatment. Median (95% CI) follow-up was 58.0 (48.2-69.3) months. Median RFS was 56.7 (46.9-67.4) and median OS was 58.0 (48.2-69.3) months. There was no benefit in RFS (p=0.08) for stage IA/IB patients who received adjuvant chemotherapy (Figure 1). There was a trend toward no chemotherapy being superior to adjuvant chemotherapy in OS (p=0.05). Twelve patients had recurrence. One patient recurred in a lymph node and the peritoneum, 8 had a pelvic recurrence, 2 had peritoneal recurrence only, and 1 patient with fertility sparing surgery recurred in the remaining ovary. Three patients were salvageable at the time of recurrence and are alive with no disease. Conclusions: Patients with Stage I, G1 and G2 EnOC have excellent prognosis and staging lymphadenectomy does not improve RFS or OS. Morover, patients with stage IA/IB who did not have complete staging lymphadenectomy, did not benefit from adjuvant chemotherapy. Download : Download high-res image (70KB) Download : Download full-size image

Objectives: Same-day discharge (SDD) after minimally invasive hysterectomy for benign or malignant gynecologic conditions has been shown to be safe and feasible, but remains challenging to implement. We designed and implemented a quality improvement perioperative program for minimally invasive gynecologic oncology surgery (MIGOS). Our aim was to improve SDD rate from 30% to 75% over the study period, while maintaining acceptable 30-day perioperative outcomes and patient experience. Methods: Consecutive patients undergoing minimally invasive hysterectomy at a single cancer centre were included during the 9-month project period and a historical cohort of 100 consecutive patients was identified for comparison. A team of gynecologic oncologists, anesthesiologists, and nurses developed a comprehensive perioperative care program and met bi-weekly to revise interventions through plan-do-study-act (PDSA) cycles. Patients were followed for 30 days after discharge. We conducted a descriptive analysis of the characteristics of pre-MIGOS and MIGOS patient cohorts using Wilcoxon rank-sum or Fisher exact tests. We used a run chart to monitor effects of interventions on outcomes and a pre-post analysis to evaluate for statistical significance of change in SDD and perioperative outcomes. Results: We assessed 100 consecutive pre-MIGOS and 79 consecutive MIGOS patients. Overall SDD rates increased from 31% (31/100) to 71% (56/79) after implementation (p Download : Download high-res image (130KB) Download : Download full-size image Conclusions: Following implementation of a perioperative quality improvement program targeted towards minimally invasive gynecologic oncology surgery, a multidisciplinary team significantly improved SDD rates while maintaining low 30-day perioperative complications and excellent patient experience.

5543 Background: High grade serous ovarian cancers (HGSC) with BRCA mutation are biologically unique, with distinct molecular and clinical behaviour from sporadic cases. It is unclear if these biological differences translate to favorable outcomes at the time of primary cytoreductive surgery (PCS). The aim of this study is to compare the amount of residual disease following PCS in BRCA-mutated (BRCAm) and wildtype (BRCAwt) HGSC, and to assess whether BRCA status is an independent predictor of residual disease. Methods: We conducted a retrospective analysis of patients with HGSC with known germline and somatic BRCA mutation status, treated with PCS from 2000 to 2017. We compared the cytoreduction outcomes between the BRCAm and the BRCAwt cohorts and built a predictive model to assess whether BRCA status was associated with amount of residual disease at the time of PCS. Results: Of 355 women, 144 harbored germline or somatic BRCA mutations (41%) and 211 were BRCAwt (59%). BRCAm women tended to be younger (54 vs. 59; p < 0.001), but there were no differences between the two groups in stage, disease burden at presentation, surgical complexity score, length of surgery, or perioperative complications. The BRCAm group had a higher rate of complete cytoreduction to no residual disease (0mm) [75% vs. 54%], and a lower rate of optimal cytoreduction (1-9mm) [16% vs. 34%] or suboptimal cytoreduction (≥10mm) [9% vs. 12%] (p < 0.001). In our predictive model, after accounting for length of surgery, CA-125 level, stage, disease scores and surgical complexity scores, BRCAm status was predictive of complete cytoreduction to 0mm residual disease (OR 4.78; 95% CI 2.32-9.85; p < 0.001). Conclusions: BRCA status is predictive of complete cytoreduction at time of PCS in HGSC. Timely availability of BRCA testing is paramount as it may aid in the therapeutic decision making between PCS or neoadjuvant chemotherapy in women with newly diagnosed HGSC.

BACKGROUND The objective of this study was to determine the cost-effectiveness of radical hysterectomy (RH) and sentinel lymph node biopsy (SLNB) for the management of early-stage cervical cancer (stage IA2-IB1). METHODS A simple decision tree model was developed to follow a simulated cohort of patients with early-stage cervical cancer treated with RH and 1 of 3 lymph node assessment strategies: systematic pelvic lymph node dissection (PLND), SLNB using technetium 99 (Tc99) and blue dye, and SLNB using Tc99 only. SLNB using indocyanine green (ICG) was used as an exploratory strategy. Relevant studies were identified to extract the probability data and utility parameters and to estimate quality-adjusted life-years (QALYs) and absolute life-years (ALYs). Only direct medical costs were modeled, and the time horizon for the study was 5 years. RESULTS SLNB using Tc99 and blue dye cost $21,089 and yielded 4.54 QALYs and 4.90 ALYs. PLND cost $22,353 and yielded 4.47 QALYs and 4.91 ALYs. SLNB using blue dye and Tc99 was the most cost-effective strategy when ALYs were considered with an incremental cost-effectiveness ratio (ICER) of $144,531. When QALYs were considered, the SLNB technique using Tc99 and blue dye dominated all other strategies. SLNB using ICG cost $20,624 and yielded 4.90 ALYs and 4.54 QALYs. It was clinically superior to and less expensive than all other strategies when QALYs were the outcome of interest and had an ICER of $221,171 per ALY in comparison with RH plus PLND. CONCLUSIONS SLNB using Tc99 and blue dye with ultrastaging is considered the most cost-effective strategy with respect to 5-year progression-free survival and morbidity-free survival. Although it was included only as an exploratory strategy in this study, SLNB with ICG has the potential to be the most cost-effective strategy. Cancer 2017;123:1751–1759. © 2017 American Cancer Society.

Objective To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Methods Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. Results 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44–1.63) p =0.63) or overall survival (OS) (0.84 (0.39–1.82) p =0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55–2.54) or O S(HR 1.04 (95% CI: 0.40–2.69)). Conclusion Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients.

Objectives Ovarian clear cell carcinoma (OCCC) has unique clinical and molecular features compared to other epithelial ovarian cancer histologies. Our objective was to describe the incidence of secondary malignancies (SM) in patients with OCCC. Methods Retrospective cohort study of patients with pure OCCC at two tertiary academic centres in Toronto, Canada between 1995–2017. Demographic and histopathologic details were obtained from chart review and confirmed with a provincial cancer registry. Results Of 209 patients with OCCC, 53 developed a SM (25.4%), of whom 7 developed 2 SM. SM included: breast (13), skin (10), gastrointestinal tract (9), other gynecologic malignancies (8), thyroid (6), lymphoma (5), head and neck (4), urologic (3) and lung malignancies. Thirty-five SM occurred before index OCCC (median 9.4 years before), 21 after OCCC (median 5.8 years after), and 4 were diagnosed concurrently. More patients with SM had a smoking history that those without SM (28.3% vs 11.5%, p=0.004). Other demographic characteristics were similar between groups (age (56 vs 54, p=0.23), body mass index (25.7 vs 25.5, p=0.70), diabetes (5.7% vs 5.8%, p=0.76), proportion of patients of Asian ethnicity (18.9% vs 23.1%, p=0.66)). The proportion presenting with stage I OCCC was comparable (66% vs 59%, p=0.46). Only one patient had documented Lynch syndrome. Survival analysis is pending. Conclusions Patients with OCCC are at increased risk of SM, most frequently non-Lynch syndrome related. This could suggest that a subset of patients with OCCC harbor mutations rendering them susceptible to SM. SM that could be associated with Lynch syndrome warrants genetic testing.

The PROMISE diagnostic algorithm, which uses p53, mismatch repair (MMR) protein immunohistochemistry, and DNA polymerase e (POLE) exonuclease domain mutation testing, is a reliable surrogate of the molecular group in endometrial carcinoma. Its prognostic value has been validated in endometrial carcinoma and ovarian endometrioid carcinoma. Moreover, a similar prognostic grouping has been recently documented in endometrial clear cell carcinoma. Thus, we aimed to explore the role of these markers in ovarian clear cell carcinoma, another endometriosis-associated malignancy. A total of 90 cases were identified and confirmed after secondary review. Immunohistochemistry for p53, MLH1, MSH2, MSH6, and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. POLE mutational analysis was performed in 47 cases. Results were correlated with clinicopathologic variables including disease-free survival (DFS), overall survival, and disease-specific survival (DSS). Endometriosis was found in 67 (74%) cases. Six (7%) tumors were p53 abnormal, 82 (91%) were p53 normal, and 2 (2%) tumors had MMR deficiency (1 MSH6 loss and 1 MSH2/6 loss; both were p53 normal). Several POLE variants of unknown significance were detected, but no pathogenic mutations. The mean follow-up period was 43 months (median: 34, range: 1 to 189). Abnormal p53 status was associated with advanced Federation of Gynecology and Obstetrics stage, lymph node metastases, DFS and DSS (P

BACKGROUND Embryonal rhabdomyosarcoma of the cervix is a rare and aggressive malignancy that usually affects children and young adults. CASE We describe a 2-year-old patient who presented with a mass protruding through the vaginal introitus. Preoperative investigations including vaginoscopy, hysteroscopy, magnetic resonance imaging, and biopsies confirmed embryonal rhabdomyosarcoma, botryoid subtype, arising from the cervix. She was successfully treated with neoadjuvant chemotherapy and interval laparoscopic radical trachelectomy to achieve remission. CONCLUSION Collaboration between the pediatric and adult surgical and medical oncology teams was critical to implement this fertility-sparing treatment strategy in such a young girl having this rare tumor.

High-grade serous ovarian carcinoma (HG-SOC) is the most common subtype of ovarian cancer and has the worst prognosis. There is intense controversy on whether the temporal order of cytoreductive surgery and chemotherapy affects treatment outcome, with the main options being primary debulking surgery with adjuvant chemotherapy (PDS) versus neo-adjuvant chemotherapy with interval debulking surgery (NACT). Although some studies report that PDS-treated patients survive significantly longer than those receiving NACT, other reports showed no significant difference in patient outcome. To address this question in an unbiased way, we used computational modeling and simulated HG-SOC progression dynamics with different treatments. We developed a mathematical framework to predict the evolution of chemotherapy resistance, and populated our model with survival data from >300 patients receiving PDS or NACT. After estimating the rates of proliferation and mutation of carcinoma cells, we determined that most HG-SOC patients likely harbor chemotherapy-resistant cancer cells at diagnosis. Furthermore, we predicted the effects of PDS and NACT on the number of sensitive and resistant cells, as well as patient survival following treatment, and found that our model closely recapitulated clinical observations in both training and test sets. Based on our results, we predict that PDS with optimal debulking ( Finally, we evaluated the potential benefits of early diagnosis of naïve or relapsed HG-SOC. We recapitulated the clinical finding that CA125-based earlier diagnosis of relapsed cancer does not improve survival. We also predict that more sensitive detection methods (such as ctDNA-based diagnosis) are unlikely to improve survival post-relapse with current chemotherapy, because earlier diagnosis does not decrease the number of chemo-resistant cells, which are already enriched at recurrence. By contrast, our model predicts that with sufficiently sensitive assays, early detection could improve survival time and increase chances of cure. Citation Format: Shengqing Gu, Stephanie Lheureux, Azin Sayad, Liat Frida Hogen, Iryna Vyarvelska, Paulina Cybulska, Marcus Bernardini, Barry Rosen, Amit Oza, Benjamin G. Neel. Computational modeling of serous ovarian carcinoma dynamics: Implications for screening and therapy. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-06.

Introduction Borderline ovarian tumors are typically indolent neoplasms. Since many are diagnosed in younger women, fertility conservation is an important consideration and has been advocated based on retrospective data. The objective of this study was to identify features impacting on recurrence and survival in a series of borderline ovarian tumors, and to assess the safety of a fertility-sparing approach. Material and methods A historical cohort study of consecutive borderline ovarian tumors cases treated at a single institution over 30 years (1981–2011). Data on surgical approach (fertility-sparing or otherwise), disease stage, CA125 levels, histological features, adjuvant treatment and follow-up data were collected. Recurrence and survival were assessed using the Kaplan–Meier method and associations with the variables of interest were evaluated using a multivariate Cox proportional hazards model. Results 213 patients were included. Of 132 women age 40 years and below at diagnosis, 112 (85%) had a fertility-sparing procedure and 60 (46%) had conservation of an involved ovary. Fifty patients (24%) developed recurrences; fertility preservation (hazard ratio = 2.57; 95% confidence interval 1.1–6; p = 0.029) and advanced stage (hazard ratio = 4.15; 95% confidence interval 2.3–7.6; p < 0.001) were independently associated with recurrence on multivariate analysis. Eleven (5%) patients died of their disease. Fertility preservation was not associated with compromised survival. Conclusions Borderline ovarian tumors carry a good prognosis overall. Fertility preservation is associated with a higher risk of disease relapse; however, as most relapses are localized and may be salvaged with surgical treatment, overall survival is not compromised.

Objective To assess the impact of adjuvant chemotherapy on survival in patients with surgical stage I ovarian clear cell carcinoma (OCCC). Methods Data collection and analysis of surgical stage I OCCC patients treated at two tertiary cancer centers was performed. Descriptive statistics, univariate and multivariable analyses and Kaplan-Meier survival probability estimates were completed. Results Sixty stage I OCCC patients who underwent comprehensive surgical staging were identified. 29 patients received adjuvant chemotherapy and 31 did not. Median follow-up was 4.96 (0.4–16.4) years. The 5-year disease specific survival (DSS) was 84.2%: 95% for stage IA and 76% for stage IB+IC (p=0.16). There were 11 disease specific deaths: 7 in the no adjuvant chemotherapy group (NACG) and 4 in the adjuvant chemotherapy group (ACG). 5-year DSS was 84.2%: 74% in NACG and 93% in ACG, (p=0.13). Seventeen patients recurred: 11 in NACG and 6 in ACG (p=0.2). None of the 21 patients with stage I known negative cytology recurred. 5-year PFS was 74%: 58% in NACG and 86% in ACG (p=0.035). On univariate analysis, no-adjuvant chemotherapy and positive cytology were poor prognostic factors for PFS: HR=2.36, p=0.04 and HR=3.1, p=0.027, respectively. After adjusting for positive cytology, no-adjuvant chemotherapy was still found to significantly correlate with a worse PFS (HR=4, p=0.01). Conclusion Our data supports the use of adjuvant chemotherapy for surgical stage I OCCC. As no patients in our cohort with surgical stage I known negative cytology recurred, more research on the benefit of adjuvant chemotherapy in this group is warranted.

ObjectiveThe objective of this study was to evaluate the effect of treatment delay on prognosis in patients with cervical cancer.MethodsThe study group of this historic cohort study comprised 321 patients newly diagnosed with cervical cancer between 1999 and 2010. Time from diagnosis to treatment was analyzed both as a continuous variable and as a categorical variable in 3 groups that differed in waiting time between diagnosis and treatment initiation: 30 days or less (group 1, n = 134), 30 to 45 days (group 2, n = 86), and more than 45 days (group 3, n = 101). Associations between waiting time group, patients’ characteristics, and disease outcome were investigated usingttests, analyses of variance and Cox regression analyses, Kaplan-Meier survival analysis, and log-rank (Mantel-Cox) tests.ResultsTime from diagnosis to treatment initiation, when analyzed as a continuous variable, was not a significant factor in survival. There were no between-group differences in age, smoking rate, marital status, gravidity, parity, tumor histology, or lymph node involvement. Early-stage disease and small tumor diameter were diagnosed most frequently in group 3. However, there was no significant between-group difference in 3-year survival rates (74.6%, 82.2%, and 80.8% in groups 1, 2, and 3, respectively;P= 0.38). On multivariate analysis, only stage, histology, and lymph node involvement were significant prognostic factors for survival. Before starting treatment, 28 patients underwent ovarian preservation procedures.ConclusionsLonger waiting time from diagnosis to treatment was not associated with worse survival. Our findings imply that if patients desire fertility or ovarian preservation procedures before starting treatment, it is acceptable to allow time for them.