To characterize the effect of transversus abdominis plane (TAP) blocks on opioid use and pain score in the first 48 hours following laparotomy for gynecologic malignancy

Objectives Accumulating evidence correlates myocardial injury after noncardiac surgery(MINS), even when asymptomatic, with increased cardiac and non-cardiac morbidity and mortality. There is no literature on MINS specific to Gynecologic Oncology. We sought to evaluate the incidence and risk factors of MINS in patients aged ≥70. Methods Elective laparotomies between 01/2016–09/2020 for patients aged≥70 at a tertiary hospital in ON, Canada, were reviewed using prospectively-collected National Surgical Quality Improvement Program(NSQIP) data. MINS was defined as peak serum high-sensitivity troponin-T concentration≥0.04ng/mL within 30 days postoperatively. Logistic regression analysis was performed. Results In this cohort of ­­258 patients, of 242(93.8%) who underwent postoperative troponin screening, 40(16.5%) experienced MINS without exhibiting ischemic symptoms or ECG changes. The diagnosis of MINS led to a change in cardiovascular medications for 35 patients(87.5%). On univariate analysis, Revised Cardiac Risk Index(RCRI) of 3–5(p=0.002), history of coronary artery disease(p=0.003) or insulin-dependent diabetes(p=0.006), preoperative use of antiplatelets(p=0.009), beta-blockers(p=0.02), ACE-inhibitors(ACEI) or angiotensin-receptor blockers(ARB)(p=0.020) and frailty as defined by the NSQIP modified frailty index-5(p=0.02), were associated with greater risk of MINS. Factors reflecting surgical complexity including surgical complexity score, operative duration, blood loss and advanced oncologic stage, were not predictive. Multivariable analysis using backward selection procedure identified elevated RCRI and preoperative ACE/ARB as significant risk factors(OR5.93,95%CI 1.52–23.31,p=0.01 and OR2.3,95%CI 1.18–5.06,p=0.02). Conclusions One in 6 patients in our cohort experienced asymptomatic MINS, irrespective of surgical complexity. MINS may be underdiagnosed after Gynecologic Oncology surgery in the absence of systematic troponin screening. Our analysis highlights a possible opportunity to optimize cardiac risk factors and potentially reduce morbidity and mortality.

e22525 Background: Ovarian cancer (OC) is the third most common Lynch syndrome (LS)-associated cancer in women but there is no established screening strategy to identify LS in this population. An adequate family history may identify patients suspected of LS, prompting a referral to genetic assessment. We have previously validated the 4-item brief Family History Questionnaire (bFHQ) in endometrial cancers. The objective of this study was to assess whether bFHQ can be used as a screening tool to identify women with OC at risk of LS. Methods: Prospective cohort study recruited women with newly diagnosed non-serous/non-mucinous OC from three cancer centers in Ontario, Canada. Participants completed bHFQ, extended Family History Questionnaire (eFHQ; encompassing Amsterdam II criteria, Society of Gynecologic Oncology 20-25% criteria and Ontario Ministry of Health criteria), immunohistochemistry (IHC) for mismatch repair (MMR) proteins and universal germline testing for LS. The performance characteristics were compared between bFHQ, eFHQ, and IHC. Results: Of 215 participants, 169 (79%) were evaluable with both bFHQ and germline mutation status; 12 of these 169 were confirmed to have LS (7%). Nine of 12 patients (75%) with LS were correctly identified by bFHQ, compared to 6 of 11 (55%) by eFHQ and 11 of 13 (85%) by IHC. The sensitivity, specificity, positive predictive values and negative predictive values of bFHQ were 75%, 66%, 15% and 98%, compared to 55%, 92%, 35% and 96% for eFHQ and 85%, 90%, 39% and 99% for IHC respectively. IHC was the most sensitive and specific approach. The 4-item bFHQ was more sensitive than eFHQ and took less than 10 minutes for each patient to complete. Conclusions: Patient-administered bFHQ may serve as an adequate screening tool to triage women with OC for further genetic assessment for LS, especially in centers without access to universal tumor testing for IHC for MMR.[Table: see text]

Objectives Undifferentiated and dedifferentiated endometrial carcinomas (UEC/DDEC) are rare, high grade, and have only been increasingly recognized within the past decade. Studies of their behavior and response to adjuvant to guide prognostication and management are limited. We present the management experience of a single institution. Methods Using the Juravinski Hospital electronic medical record, we identified all patients with UEC or DDEC treated at our institution from January 2005-December 2020. Clinical information was obtained by chart review. Results We identified 35 patients with UEC/DDEC; 15 UEC, 20 DDEC. Mean age was 66 years. Only 25.1% had preoperative endometrial biopsy concordant with final pathology despite 87.5% review by gynecologic pathologists. Stage distribution was 37.1% stage I, 14.3% stage II, 14.3% stage III, 34.3% stage IV. 7/33 (21.2%) had gross residual after surgery; 4 received adjuvant carboplatin-paclitaxel chemotherapy with 2 progressions, 1 partial response and 1 complete response (ORR 50%). Mean PFS was 11.7±9.3 months. Fifteen patients had progressive or recurrent disease—of these, 4 were treated with radiation, 3 with chemotherapy (adriamycin, carboplatin-paclitaxel, doxorubicin), and all 7 progressed on treatment. The most common site of recurrence was widely disseminated disease (54.5%), followed by nodal (18.2%) and chest (18.2%). Mean OS was as follows by stage: stage I-II completely resected, 43 months; stage III completely resected, 19 months; stage IV, suboptimally debulked or inoperable, 20 months. Conclusions UEC/DDEC are aggressive tumours with poor prognoses and remain challenging to diagnose on preoperative biopsy. Platinum-based adjuvant chemotherapy may have some efficacy, however, recurrences respond poorly to salvage.

Objective: Synchronous endometrial and ovarian cancers are reported in 5%–10% of endometrial or ovarian cancers, but the incidence of Lynch syndrome and the optimal strategy to identify it is not well established in this population. Most centers favor reflex mismatch repair (MMR) testing of the endometrial cancer only. We aim to examine the proportion of cases that are MMR-deficient (MMRd) or microsatellite-instable (MSI-H) in the endometrium and ovary and assess the concordance between the 2 tumor sites.

Background For women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In the current study, the authors compared the performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for the detection of LS. Methods Women with nonserous and/or nonmucinous ovarian cancer were recruited prospectively from 3 cancer centers in Ontario, Canada. All underwent germline testing for LS and completed a family history assessment. Tumors were assessed using MMR IHC and MSI. The sensitivity, specificity, and positive and negative predictive values of screening strategies were compared with the gold standard of a germline result. Results Of 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (MSH6); 3 women with mutL homolog 1 (MLH1); 2 women with PMS1 homolog 2, mismatch repair system component (PMS2); and 1 woman with mutS homolog 2 (MSH2). A total of 28 women had MMR-deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (withMLH1promoter methylation analysis on MLH1-deficient tumors) followed by MSI for nonmethylated and/or MMR-intact patients was the most sensitive (92.3%; 95% confidence interval, 64%-99.8%) and specific (97.7%; 95% confidence interval, 94.2%-99.4%) approach, missing 1 case of LS. IHC withMLH1promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%. Conclusions Sequential IHC (withMLH1promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC withMLH1promoter methylation analysis also performed well and is likely more cost-effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS.

Objective: Despite recommendations for reflex immunohistochemistry (IHC) for mismatch repair (MMR) proteins to identify Lynch syndrome (LS), uptake of genetic counselling by those who meet referral criteria is low. Our objective was to use a multipronged approach including a genetics navigator to increase uptake of genetic testing for LS in endometrial (EC) and nonserous/mucinous ovarian cancer (OC) patients.

Objectives There is no established screening strategy for Lynch syndrome (LS) in synchronous endometrial (EC) and ovarian cancers (OC). Most centers use mismatch repair (MMR) immunohistochemistry (IHC) on endometrium only. We aim to examine the concordance in MMR expression between tumor sites in synchronous EC/OC. Methods Thirty women with newly diagnosed synchronous EC/OC were prospectively recruited from three cancer centers in Ontario, Canada. Tumor sites were assessed for MMR deficiency by IHC and MSI testing. All women underwent germline testing for MMR mutations. Results Out of 30 cases, twelve cases (40%) were either MMRd or MSI-H, with 5 (17%) confirmed to have a pathogenic germline mutation: 3 MSH6, 1 MLH1 and 1 PMS2. MMR testing by IHC took place in both ovary and endometrium in 27 cases and results were discordant between two sites in 2 cases (7%). MSI testing in both sites took place in 24 cases, and results were discordant in 2 cases (8%). Out of the 5 cases with confirmed LS, performing IHC alone on endometrium would have missed the diagnosis in 1 case, and performing MSI testing alone on endometrium would have missed the diagnosis in 3 cases, which all had a MSH6 mutation. One case of LS was missed by both IHC and MSI testing. Conclusions The incidence of LS was high in women with synchronous EC/OC (17%). Given the discordance in IHC and MSI results at the two tumor sites, consideration should be given to direct germline testing in all cases of synchronous EC/OC.

Adjuvant treatment for stage II endometrial adenocarcinoma may include vaginal vault brachytherapy (VBT) alone, external beam radiotherapy (EBRT) alone or combination treatment. Recommendations from SGO, NCCN, ASTRO & ESMO have supported the use of external beam with or without VBT. The role of surgical lymph node staging and optimal adjuvant therapy are unclear. We aim to examine a contemporary cohort of patients treated at our Canadian center to determine which factors may affect rate and site of recurrence in stage II endometrioid adenocarcinoma. We retrospectively reviewed the charts of 166 patients who had surgery in our Canadian Local Integrated Health Network (LIHN) between 2004 and 2014 with pathologic stage II endometrioid adenocarcinoma per FIGO 2009 staging. Demographics, histology, treatment, and follow-up data were collected. Thirteen patients received adjuvant treatment and follow-up outside of our LIHN and were therefore not able to be included in analysis. Univariate analysis was performed to identify prognostic factors for recurrence and then those found to be significant were analyzed using multivariate cox regression analysis. One hundred and forty-five patients underwent simple hysterectomy (94.8%) and 66 patients had a pelvic lymph node dissection (43.0%). Adjuvant treatment included EBRT with or without VBT (n=103, includes two patients who also received chemotherapy), VBT alone (n=38), and no adjuvant treatment (n=12). Twenty percent (31/153) of patients recurred. Mean time to recurrence was 19 months (range: 1-70 months). Recurrence occurred in 18.4% (19/103) of patients treated with EBRT +/- VBT (one of whom also had chemotherapy), 21.1% (8/38) treated with VBT alone, and 33.3% (4/12) of those who had no adjuvant treatment. Local recurrence occurred in 9 patients (5.8%), 15 patients had distant metastasis at time of recurrence. Clinical characteristics of patients who recurred were evaluated. Lymphovascular space invasion (LVSI) trended towards significance (p=0.055). Only depth of myometrial invasion > 50% was significant (p=0.007) and predicted recurrence with a hazard ratio of 4.40 (1.52-12.70). There was no significant difference in recurrence free survival between EBRT+/-VBT (134.0 months CI: 122.5-146.0), VBT alone (108.0 months CI: 92.0-123.5) and no adjuvant treatment (61.5 months CI: 47.0-76.0). Our study supports existing evidence that myometrial invasion is a significant predictor for recurrence in endometrial cancer. Despite a trend towards improved recurrence free survival in patients who received adjuvant treatment, we did not detect a significant difference between different adjuvant modalities. A larger sample and prospective study is needed to confirm whether brachytherapy alone could be offered safely as adjuvant treatment in this setting, particularly in surgically staged patients with less than 50% myometrial invasion and without LVSI.

Serous adenocarcinoma is a rare aggressive histologic subtype of endometrial cancer with a high rate of recurrence and a poor prognosis even at early stages. The optimal approach to adjuvant treatment for early stage disease is unknown. Patients with endometrium limited disease and a complete lymphadenectomy are presumed to be at lower recurrence risk. We report on the pathologic and treatment characteristics of recurrent cases in a large cohort of serous endometrial cancer patients to investigate whether adjuvant therapy can be omitted in low risk cases. A retrospective chart review inclusive of all cases of "serous carcinoma" of the endometrium from 2000-2014 was completed. Patients with FIGO 2009 stage IA pure or mixed serous histology who had undergone total hysterectomy and bilateral salpingo-oophorectomy were included. Kaplan-Meier estimates were calculated for overall survival (OS) and recurrence free survival (RFS) and hazard ratios for prognostic factors were calculated using Cox proportional hazards modeling. There were 63 patients with FIGO Stage 1A disease. Median follow up was 30.2 months. Patients were observed (N = 33) or received adjuvant treatment (chemotherapy plus brachytherapy N = 21; chemotherapy alone N = 7; or pelvic radiation therapy +/- chemotherapy N = 2). Fifty-seven patients (80.2%) had pelvic lymphadenectomy (median 9 nodes). Thirty-two (32) patients had endometrium-confined disease. There were seven recurrences (11.1%), at a median of 11 months (range 8-35). At 2- and 5-years RFS was 89.3% and 85.8%; and OS was 92.7% and 87.6%, respectively. Of those patients observed, four (12.1%) developed recurrence, with 2 vaginal recurrences only. In patients with endometrium-confined disease 9% developed recurrence, none of whom received adjuvant therapy. Two of 29 patients treated with chemotherapy as a component of their adjuvant treatment developed recurrence (6.9%). The majority of patients who recurred had extrapelvic recurrence with or without locoregional recurrence (71.4%). More than half of patients who recurred did not have adequate pelvic lymph node assessment (4 of 7 cases). On multivariate analysis only presence of myometrial invasion (HR 1.41, P = 0.63) and presence of lymphovascular invasion (HR 2.69, P = 0.29) were associated with inferior RFS, however, these were not statistically significant. In our cohort of early stage serous endometrial cancers RFS and OS were inferior to those reported for patients with endometriod histology. Our study indicates the importance of adequate surgical staging in early stage disease and supports the use of combination chemotherapy and brachytherapy in adjuvant treatment, even in patients with endometrium-confined Stage 1A disease.

Results: We identified 22 patients with the diagnosis of undifferentiated endometrial cancer. Medium age was 65 years. Obesity was common, with medium body mass index of 30. Slightly over half (12/22) were diagnosed at stage III or IV. Common metastatic sites were nodal (9/12 patients), hematogenous (6) and intraperitoneal (6). Just 4/12 patients were fit enough to undergo treatment for metastatic disease. None responded to platinum based chemotherapy given as first line treatment or to Doxorubicin as second line treatment, and in fact developed rapidly progressive disease. External beam radiation was used in 2 patients with metastatic disease: one had stable disease within the radiation fields region but developed distant disease within 2 months, the second patient had progressive disease within the radiation fields. Overall survival was 14 months for all patients, and 6 months for patients with stage 3 or 4 disease.

Objective: Controversy exists regarding the best chemotherapy regimen for women with low-risk gestational trophoblastic neoplasia (GTN) with World Health Organization scores of 0-4. Since virtually all patients are cured, cost and quality of life are important factors. We constructed a probabilistic decision analysis model to evaluate the cost and outcomes for 4 commonly used chemotherapy regimens.

Objective: The choice of adjuvant treatment for patients with high-risk endometrial adenocarcinoma is controversial. This study sought to evaluate the association between risk of recurrence and both primary tumor factors and treatment received.

The treatment of cervical cancer has seen great advances since the first radical hysterectomy was performed by Ernst Wertheim in 1898. Breakthroughs in surgical techniques, including total laparoscopic approaches, sentinel lymph node mapping, and fertility-sparing procedures have dramatically reduced the morbidity of definitive treatment, while preserving oncologic outcomes. Increasingly conservative approaches are being proposed, based on individual patient and tumour characteristics. Cervical cancer was previously thought to be chemo-resistant, and therefore chemotherapy was used only for recurrent or metastatic disease. However, after responses were noted to platinum-based regimens (Friedlander et al., 1983, 1984), interest in the use of chemotherapy was reignited, particularly in the neoadjuvant setting. Whether prior to surgery or radiotherapy, the use of neoadjuvant chemotherapy in cervical cancer has been actively studied, in multiple settings and diverse patient populations, showing promise with acceptable toxicity profiles. In this chapter, the use of neoadjuvant chemotherapy in the treatment of cervical cancer will be reviewed. The rationale will be explored followed by the evidence for its effectiveness prior to surgery, radiotherapy, and fertility-sparing procedures. An approach to patient selection will be provided, and chemotherapeutic regimens will be compared, concluding with areas of ongoing and future research.