The five-factor modified frailty index predicts adverse postoperative and chemotherapy outcomes in gynecologic oncology.

INTRODUCTION: Frailty is increasingly recognized as a predictor of postoperative morbidity and oncologic outcomes. Evidence of the predictive value of frailty assessment in gynecologic oncology remains sparse. OBJECTIVES: To evaluate the National Surgical Quality Improvement Program (NSQIP) comorbidity-based modified Frailty Index-5 (mFI-5) as predictor of severe postoperative complications, non-completion of chemotherapy and other patient-centered outcomes in gynecologic oncology patients >70 years-old undergoing surgery. METHODS: Prospectively-collected NSQIP data and retrospective chart review of patients undergoing elective laparotomies for gynecologic malignances at a tertiary academic center in Ontario, Canada, between 01/2016-09/2020 were reviewed. Primary outcome was rate of 30-day Clavien-Dindo (Clavien) grade III-V complications. Secondary outcomes included Clavien II-V complications, postoperative length of stay (LOS), non-home discharge and non-completion of chemotherapy. Logistic regression analyses and receiver-operator curves were performed. RESULTS: Two-hundred and fifty-nine patients were included; 103 were planned to receive adjuvant chemotherapy. Fifty-three patients (20.5%) had an mFI ≥ 2 and were categorized as frail. On multivariable analyses, frailty independently predicted grade III-V complications (OR 24.49, 95%CI 9.72-70.67, p < 0.0001), grade II-V complications (OR 4.64, 95%CI 2.31-9.94, p < 0.0001), non-home discharge (OR 7.37, 95%CI 2.81-20.46, p < 0.0001), LOS ≥ 7d (OR 3.6, 95% CI 1.54-8.6, p = 0.003) and non-completion of chemotherapy (OR 8.42, 95%CI 2.46-32.79, p = 0.001). Adjusted C-statistics demonstrated strong predictive value of the mFI-5 for grade III-V (0.92, 95%CI 0.86-0.97) and grade II-V (0.74, 95%CI 0.68-0.8) complications as well as non-home discharge (0.86, 95%CI 0.78-0.95) and chemotherapy non-completion (0.87, 95%CI 0.8-0.95). CONCLUSION: Frailty as assessed with the mFI-5 predicted adverse postoperative and chemotherapy outcomes in gynecologic oncology patients aged ≥70 undergoing a laparotomy. The mFI-5 is a concise tool that can be used for routine frailty screening and risk stratification.

Gender imbalance in gynecologic oncology authorship and impact of COVID-19 pandemic.

OBJECTIVE: Despite increased participation of women in academic medicine in recent decades, gender disparities persist. The gender gap in authorship and editorial boards in gynecologic oncology, and impact of the COVID-19 pandemic, have not been recently evaluated. We examined gender representation and the impact of COVID-19 on authorship and editorial boards of two major peer-reviewed gynecologic oncology journals. METHODS: We conducted a bibliometric analysis of original articles published in Gynecologic Oncology and the International Journal of Gynecological Cancer, comparing the most contemporary 5-year period (2016-2020) to single years in the two prior decades (1996, 2006). To assess the early impact of COVID-19, we compared publications from May 2020-April 2021 to 2019. Editorial boards were analyzed for gender composition. First names, pronouns, and institutional photographs were used to determine gender. RESULTS: There were 3022 original articles published between 2016 and 2020, 763 in 2006, and 203 in 1996. Gender was identified for 91.3% of first authors (3641 articles) and 95.6% of senior authors (3813 articles). Men comprised the majority of the editorial boards in 2021 at 57% and 61% for Gynecologic Oncology and the International Journal of Gynecological Cancer, respectively. Men were overrepresented as senior authors across all study periods: 93% in 1996, 77% in 2006, and 58% in 2016-2020. Over time, representation of women as first and senior authors increased (7% in 1996, 42% in 2016-2020, p<0.00001). There was no immediate impact of the early pandemic on gender distribution of authorship. CONCLUSIONS: Despite greater representation of women over time as authors in gynecologic oncology journals, there remains gender disparity in senior authorship and editorial board representation. This presents an opportunity for the academic publishing community to advocate for deliberate strategies to achieve gender parity. Although no impact of the early COVID-19 pandemic was found, this requires ongoing surveillance.

Dual mechanical and pharmacological thromboprophylaxis decreases risk of pulmonary embolus after laparotomy for gynecologic malignancies.

OBJECTIVES: Patients with gynecologic malignancies have high rates of post-operative venous thromboembolism. Currently, there is no consensus for peri-operative thromboprophylaxis specific to gynecologic oncology. We aimed to compare rates of symptomatic pulmonary embolus within 30 days post-operatively, and to identify risk factors for pulmonary embolus. METHODS: The Division of Gynecologic Oncology at Sunnybrook Health Sciences Centre implemented dual thromboprophylaxis for laparotomies in December 2017. We conducted a prospective study of laparotomies for gynecologic malignancies from December 2017 to October 2018, with comparison to historical cohort from January 2016 to November 2017 using the institutional National Surgical Quality Improvement Program database (NSQIP). Pre-intervention, patients received low molecular weight heparin during admission and extended 28-day prophylaxis was continued at the surgeon's discretion. Post-intervention, all patients received both mechanical thromboprophylaxis with sequential compression devices during admission and 28-day prophylaxis with low molecular weight heparin. RESULTS: There were 371 and 163 laparotomies pre- and post-intervention, respectively. Patient characteristics (age, body mass index, diabetes, smoking, tumor stage), rate of malignant cases, operative blood loss and duration, and length of stay were similar between groups. After implementation, pulmonary emboli rates decreased from 5.1% to 0% (p=0.001). There were more cytoreductive procedures pre-intervention (p≤0.0001) but surgical complexity scores were similar (p=0.82). Univariate analysis revealed that surgery pre-intervention (OR 4.25, 95% CI 1.04 to 17.43, p=0.04), length of stay ≥5 days (OR 11.94, 95% CI 2.65 to 53.92, p=0.002), and operative blood loss ≥500 mL (OR 2.85, 95% CI 1.05 to 7.8, p=0.04) increased risk of pulmonary embolus. On multivariable analysis, surgery pre-intervention remained associated with more pulmonary emboli (OR 4.16, 95% CI 1.03 to 16.79, p=0.045), when adjusting for operative blood loss. CONCLUSION: Dual thromboprophylaxis after laparotomy significantly reduced rates of pulmonary embolus in this high-risk patient population.

Risk of second malignancy in patients with ovarian clear cell carcinoma.

OBJECTIVE: Ovarian 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. METHODS: Retrospective 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. RESULTS: Of 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. CONCLUSION: Patients 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.

Preoperative neutrophil-to-lymphocyte ratio predicts 30 day postoperative morbidity and survival after primary surgery for ovarian cancer.

OBJECTIVE: The 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. METHODS: A 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. RESULTS: Of 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). DISCUSSION: A 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.

Impact of a preventive bundle to reduce surgical site infections in gynecologic oncology.

OBJECTIVE: To assess the impact of a surgical site infection (SSI) prevention bundle for Gynecologic Oncology patients at a large academic tertiary centre in Toronto, Canada. METHODS: A SSI prevention bundle was implemented in February 2017 including: preoperative chlorhexidine shower, prophylactic antibiotics, glycemic control, normothermia, and separate closing tray. Data were collected prospectively using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) institutional data, and chart review of surgeries between January 2016 and September 2017 was performed. The primary outcome was rate of SSIs, secondary outcomes were: superficial, deep and organ space SSIs, sepsis, wound disruption, length of stay, 30-day readmission and reoperation. Logistic regression analysis was conducted to identify predictors of SSIs. RESULTS: 339 baseline and 224 post-intervention patients were included. 53 incurred one or more SSIs: 43 superficial, 6 deep, and 14 organ-space. The bundle decreased overall SSIs by 55% (12.1% to 5.4%, p = 0.008) and superficial SSIs by 54% (9.7% to 4.5%, p = 0.023). Improvement was sustained for 6 quarters. No significant difference was found in other secondary outcomes. On multivariable analysis, surgery in the pre-bundle period, BMI ≥30, laparotomies and longer operative duration were independent risk factors for overall SSIs (OR 2.23, 95% CI 1.06-5.06, -OR 3.01, 95% CI 1.57 - 5.87, OR 3.70, 95% CI 1.56 - 10.18 and - OR 2.16, 95% 1.11 - 4.19, respectively). CONCLUSIONS: This prevention bundle successfully decreased SSIs in patients undergoing gynecologic cancer surgery. We recommend improving quality of care by wide implementation of SSI prevention bundles in Gynecologic Oncology patients.

Desmoplastic small round cell tumor involving the uterine cervix: The first reported case in the literature, and brief review of gynecologic presentations.

Background: Desmoplastic small round cell tumors are exceedingly rare, usually involve abdominal organs and predominantly affect male patients. We describe the first reported case arising from the uterine cervix and provide a summary of 20 previously reported cases involving gynecologic organs. Case: A 54 year-old was diagnosed with a rapidly growing 13 cm desmoplastic small round cell tumor of the cervix. She was treated through a multimodal approach involving neoadjuvant chemotherapy and surgery. She subsequently recurred, and this was successfully treated with radiation therapy. She is well and without evidence of disease 22 months after initial diagnosis. Conclusion: We report successful treatment through multidisciplinary and multimodal management. This can guide management of future patients as no gold-standard treatment has yet been described.