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Background In patients with advanced-stage endometrial carcinoma (eca), extended-field radiotherapy (EFRT) is traditionally delivered by the 3-dimensional conformal (3D-CRT) 4-field box technique. In recent years, the use of intensity-modulated radiotherapy (IMRT) in gynecologic cancers has increased. We compared the delivery of EFRT by the 3D-CRT and contemporary IMRT techniques. Methods After surgical staging and adjuvant chemotherapy in 38 eca patients, EFRT was delivered by either IMRT or 3d-crt. Doses to the organs at risk, side effects, and outcomes were compared between the techniques. Results Of the 38 eca patients, 33 were stage me, and 5 were stage IVB. In the IMRT group, maximal doses to rectum, small intestine, and bladder were significantly higher, and mean dose to bladder was lower (p < 0.0001). Most acute gastrointestinal, genitourinary, and hematologic side effects were grade i or u and were comparable between the groups. In long-term follow-up, only grade 1 cystitis at 3 months was statistically higher in the IMRT patients. No grade iii or iv gastrointestinal or genitourinary toxicities were observed. No statistically significant differences in overall and disease-free survival or recurrence rates were observed between the techniques. Conclusions In advanced eca patients, IMRT is a safe and effective technique for delivering EFRT to the pelvis and para-aortic region, and it is comparable to the 3D-CRT 4-field box technique in both side effects and efficacy. For centres in which IMRT is not readily available, 3D-CRT is a valid alternative. [ABSTRACT FROM AUTHOR]

Background and aims With the debate over extent of lymphadenectomy in endometrial cancer, sentinel lymph node (SLN) mapping may provide a focused approach to evaluate the most relevant lymph nodes (LN) while minimizing the complications. We evaluated SLN mapping using filtered technetium99, indocyanine green (ICG), and blue dye. Methods Prospective evaluation of 100 patients who underwent SLN mapping by using submucosal and deep stromal cervical injections of technetium99, ICG, and blue dye as part of the staging for endometrial cancer. Results 286 SLNs were mapped (2.9 per patient) in 92% of patients. The bilateral detection rate was 76%. ICG had a significantly higher SLN detection rate than blue dye in both overall (87% vs 71%, respectively; p = 0.005) and bilateral (65% vs 43%, respectively; p = 0.002) detection, but similar SLN detection rates compared to technetium99 in both overall (87% vs 88%, respectively; p = 0.83) and bilateral (65% vs 71%, respectively; p = 0.36) detection. In eight cases, the SLN was in the para-aortic area and in 14 cases in the pre-sacral, hypogastric vein, or parametrial area. In nine cases, the SLN was positive for metastasis, and in seven cases the SLN was the only positive node. One SLN was falsely negative. No complications or anaphylactic reactions occurred. Conclusion Intra-operative SLN mapping using cervical injection is feasible in patients with endometrial cancer and yields adequate detection rates. It allows mapping of SLNs in areas (pre-sacral, hypogastric vein, parametrial) not routinely sampled. Given the poorer performance of blue dye, surgeons may omit its use if a combination of ICG and technetium99 is used. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: None declared.

Objective: We aim to study association of BMI of EC patients, with the level of agreement between preoperative and postoperative tumor grade., Methods: A retrospective study. We included patients with EC diagnosed in an outpatient clinic which had surgical staging as in our division. We categorized patients into BMI categories according to the World Health Organization; (BMI < 18.5 kg/m 2 ), (BMI 18.5-24.9 kg/m 2 ), (BMI 25-29.9 kg/m 2 ), (BMI 30-34.9 kg/m 2 ), (BMI 35-39.9 kg/m 2 ), and (BMI ≥ 40 kg/m 2 ). We further dichotomized the study population for obesity, defined as BMI ≥ 30.0. We analyzed agreement between preoperative and postoperative tumor grade, stratified by patient's BMI., Results: Overall, 623 women met study inclusion criteria, with a median age of 64 [interquartile range (IQR) 57-72]. Among the study cohort, the median BMI was 30.7 [IQR 25.6-38.8], with 330 (53.0%) patients being obese. EC grade 1 was diagnosed preoperatively in 353 (56.7%), grade 3 in 148 (23.8%), and grade 2 in 122 (19.6%). Endometrioid histology was diagnosed in 463 (74.3%), serous in 78 (12.5%), mixed histotype in 51 (8.2%), clear cell in 20 (3.2%) and carcinosarcoma in 11 (1.8%). In 68.7% (n = 428), there was no change in postoperative grade, and in 24.9% (n = 155), there was upgrading of tumor, and in 6.4% (n = 40), there was a tumor downgrade. There were 3 (0.5%) cases in which no tumor was found on final pathology. The rate of no change was higher in preoperative grade 3 (89.9%) vs. grades 1 (63.5%) and grade 2 (58.2%), p < .001). There was no difference in grading agreement when obese patients were compared to non-obese, p = .248. There was no difference in grading agreement when comparing the various BMI categories, with no change proportion ranging between 58.2% in BMI 30.0-34.9 mg/kg 2 and 79.7% in BMI 35.0-39.9 mg/kg 2 , p = .104. ROC analysis of BMI as predictor of no-change yielded an area under the curve of 0.466 (95% confidence interval 0.418-0.515) with a maximal performance at a BMI of 33.8 mg/kg 2 . The agreement between preoperative and postoperative tumor grade among all patients was kappa = 0.517. The agreement did not differ when compared between obese patients (kappa = 0.456) and non-obese (kappa = 0.575)., Conclusion: Our study found no significant association between BMI and the agreement between preoperative and postoperative tumor grading in EC., Competing Interests: Declarations Conflict of interest The authors have not disclosed any competing interests. Ethical approval The study was performed in accordance with the Declaration of Helsinki and was approved by the institutional review board., (© 2024. The Author(s).)

Objective: To compare postoperative stay in octogenarians and younger patients undergoing gynecologic oncology robot-assisted surgery., Methods: A retrospective review of robot-assisted surgery in Gynecological Oncology division during 2019-2022. We included all consecutive cases. Octogenarians (age ≥80 years) and younger patients were investigated by univariable analysis for characteristics and outcome., Results: A total of 816 robot-assisted surgeries were performed, 426 (52.2%) endometrial cancer, 159 (19.5%) ovarian cancer, 27 (3.3%) cervical cancer, 35 (4.3%) endometrial intraepithelial neoplasia, and in 169 (20.7%) the final pathology was benign. There were 60 (7.4%) octogenarians and 756 (92.6%) younger patients. The proportion of patients with an American Society of Anesthesiology score greater than 2 was higher among octogenarians (66.7% vs 32.0%, P < 0.001). The median console time, surgical time, and total operation theater time were similar between groups (P = 0.303, P = 0.643 and P = 0.688, respectively). Conversion rate did not differ between groups (0.4% among younger patients vs 0% in octogenarians, P > 0.99). The median length of stay in the recovery room was similar in both groups (median 170 min, interquartile range [IQR] 125-225 min vs 170 min, IQR 128-240 min in octogenarians, P = 0.731). Length of hospital stay was similar in both age groups; median 1 day (IQR 1-1) among octogenarians versus 1 (0-1) in younger patients (P = 0.136)., Conclusion: Octogenarians undergoing robotic surgery have no increased risk of length of stay or conversion to laparotomy compared with younger patients., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: Gangliosides GD2 and GD3 have been proposed to be of significance in diagnosis of ovarian masses. We aim to study serum GD2 and GD3 gangliosides as predictors of oncological outcomes among high grade serous (HGS) ovarian cancer (OC)., Materials and Methods: A retrospective study including biobanked serum samples of HGS OC treated between 2005 and 2016. Serum GD2 and GD3 concentrations were quantified using indirect ELISA and analyzed with respect to survival., Results: Sixty patients were included. Patients with GD3>12.8 ng/mL had shorter PFS when compared to patients with lower level; median 31 vs. 67 months, p = 0.005. Patients with GD2> 7.1 ng/mL had shorter median PFS than those with lower level of (23 vs. 52 months, p = 0.024.) Patients with GD3>14.5 ng/mL had shorter OS vs. patients with lower level (median 31 vs. 70 months, p = 0.002). In a Cox regression, following adjustment for age, CA-125, disease stage and age, serum elevated GD3 was independently associated with short PFS (adjusted hazard ratio 2.0, 95 % CI 1.1-3.8, p=.024). In a separate Cox regression, elevated GD2 was independently associated with PFS (adjusted hazard ratio3.0 (1.2-7.7). p=.019. High serum GD3 and GD2 were independently associated with short OS as well., Conclusions: High levels of serum GD2 and GD3 in HGS OC were associated with shorter PFS and OS. GD3 is superior to GD2 as a biomarker for prognosis., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: We assessed the global distribution and academic, administrative and research outcomes of international fellows (IFs) trained in Canadian gynecologic oncology (GO) programs., Methods: A web-based survey was sent to IFs who completed GO training in Canada. Using the Web of science database, we identified the publication list, citation record and H-index of IFs and classified them according to their region of practice: high-income countries (HIC), middle income countries (MIC), and low-income countries (LIC)., Results: From 1996 to 2020, 81 IFs from 23 countries were trained in English-speaking (62,9%) and French-speaking Canadian universities (37,1%). Most IFs came from HIC (87,6%) and none from LIC. Only 12 IFs (14,8%) are now practicing in Canada. Of the 55 IFs who completed the survey (response rate: 67,9%), the majority (58,2%) reported working in an academic hospital and 29,1% were holding an executive position in a national scholar organization. IFs participated in mentoring residents (96.4 %) and medical students (83,6%) and 36,3% initiated a GO fellowship program in their home country. 67,3% of IFs were involved in international research collaboration and 52,7% participated in international clinical trials. The mean number of publications (22,36 vs 7,75, p = 0.007), citations (369,15 vs 45,12 p = 0.0006) and H-Index (6,88 vs 2,37 p = 0.0001) were significantly higher among IFs working in HIC compared to those in MIC. Most IFs (98,2%) recommended their Canadian GO fellowship program to a colleague from their home country., Conclusion: Most IFs trained in Canadian GO fellowship programs returned to their home countries and achieved important milestones in terms of academic, clinical and research accomplishments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Objective: We aimed to study the association between obesity and survival in ovarian cancer (OC) patients, accounting for confounders as disease stage, histology, and comorbidities., Methods: Retrospective matched case-control study of consecutive patients, with epithelial OC. Obese (body mass index [BMI] ≥ 35 kg m -2 ) patients were matched in a 1:4 ratio with patients having lower BMIs (BMI < 35 kg m -2 ) based on disease stage, cytoreduction state, tumor histology and ASA score. We compared the 3-year and total recurrence-free survival and overall survival through Kaplan-Meier survival curves and Cox proportional hazards., Results: Overall, 153 consecutive patients were included, of whom 32 (20.9%) had a BMI ≥ 35. and 121 a BMI < 35. The median follow-up time was 39 months (interquartile range 18-67). Both study groups were similar in multiple prognostic factors, including American Society of Anesthesiologists physical status, completion of cytoreduction, histology and stage of disease (p = 0.981, p = 0.992, p = 0.740 and p = 0.984, respectively). Ninety-five (62.1%) patients underwent robotic surgery and conversion rate from robotic to laparotomy was similar in both groups 2 (6.3%) in obese group vs. 6 (5.0%) in lower BMI patients, p = 0.673. During the follow-up time, the rate of recurrence was similar in both groups; 21 (65.6%) in obese group vs. 68 (57.1%), p = 0.387 and the rate of death events was similar; 16 (50.0%) in obese group vs. 49 (40.5%), p = 0.333). The 3-year OS was higher in the obese group (log rank p = 0.042) but the 3-year RFS was similar in both groups (log rank p = 0.556). Median total OS was similar in both groups 62 months (95% confidence interval 25-98 months) in obese vs. 67 months (95% confidence interval 15-118) in the lower BMI group, log rank p = 0.822. Median RFS was similar in both groups; 61 months (95% confidence interval 47-74) in obese, vs. 54 (95% confidence interval 43-64), log rank p = 0.842. In Cox regression analysis for OS, including obesity, age, laparotomy and neoadjuvant treatment - only neoadjuvant treatment was independently associated with longer OS: odds ratio 1.82 (95% confidence interval 1.09-3.05) and longer RFS: odds ratio 2.16 (95% confidence interval 1.37-3.41)., Conclusions: In the present study on consecutive cases of ovarian cancer, obesity did not seem to be associated with outcome, except for an apparent improved 3-year survival that faded away thereafter., (© 2024. The Author(s).)

We aimed to identify the trends and patterns of robotic surgery research in obstetrics and gynecology since its implementation. We used data from Clarivate's Web of Science platform to identify all articles published on robotic surgery in obstetrics and gynecology. A total of 838 publications were included in the analysis. Of these, 485 (57.9%) were from North America and 281 (26.0%) from Europe. 788 (94.0%) articles originated in high-income countries and none from low-income countries. The number of publications per year reached a peak of 69 articles in 2014. The subject of 344 (41.1%) of articles was gynecologic oncology, followed by benign gynecology (n = 176, 21.0%) and urogynecology (n = 156, 18.6%). Articles discussing gynecologic oncology had lower representation in low- and middle-income countries (LMIC) (32.0% vs. 41.6%, p < 0.001) compared with high income countries. After 2015 there has been a higher representation of publications from Asia (19.7% vs. 7.7%) and from LMIC (8.4% vs. 2.6%), compared to the preceding years. In a multivariable regression analysis, journal's impact factor [aOR 95% CI 1.30 (1.16-1.41)], gynecologic oncology subject [aOR 95% CI 1.73 (1.06-2.81)] and randomized controlled trials [aOR 95% CI 3.67 (1.47-9.16)] were associated with higher number of citations per year. In conclusion, robotic surgery research in obstetrics & gynecology is dominated by research in gynecologic oncology and reached a peak nearly a decade ago. The disparity in the quantity and quality of robotic research between high income countries and LMIC raises concerns regarding the access of the latter to high quality healthcare resources such as robotic surgery., (© 2023. The Author(s).)

Endometrial carcinoma (EC) can be divided into 4 prognostic molecular subtypes, and no specific molecular profile (NSMP) type is the most commonly occurring type (∼50%). Although described as having an intermediate to favorable prognosis, this subtype encompasses pathologically and molecularly diverse tumors. We aimed to identify factors associated with outcomes within the NSMP ECs that might be used to stratify prognosis and direct treatment. Clinicopathologic, immunohistochemical, and genetic features of a large series of NSMP EC were used to identify parameters that could identify the subset associated with a very favorable outcome (disease-specific death rate <5% at 5 years, termed low-risk NSMP). A total of 1110 NSMP ECs were profiled. In a univariate analysis, stage, grade, lymphovascular invasion, estrogen receptor (ER) and progesterone receptor (PR) expression, L1CAM overexpression, and mutations in PIK3CA were associated with disease-specific survival. Two critical features, grade and ER expression, identified a low-risk NSMP subset (grade 1-2, ER-positive [>1%], 84% of cases), which showed a 5-year disease-specific death rate of 1.6% across all stages and 1.4% within stage I. The remaining cases (high-risk NSMPs, grade 3, and/or ER-negative status) were responsible for most of the disease-specific deaths (disease-specific death rate at 5 years, 22.9%; hazard ratio compared with that of low-risk NSMPs: 16.3; 95% CI, 8.4-31.7). Within NSMP EC, the low-risk and high-risk categories were of prognostic significance independent of the stage on a multivariate analysis. Low-grade and ER-positive NSMP ECs are a homogeneous low-risk group associated with an exceptionally favorable prognosis in which de-escalation and/or endocrine therapy strategies can be applied. Grade 3 and/or ER-negative status identifies a high-risk NSMP subset, including rare high-grade histotypes (eg, clear cell, dedifferentiated, and mesonephric-like), responsible for most NSMP-related deaths. Subclassification of NSMPs allows for the category of low-risk EC molecular subtypes to be dramatically expanded because it now includes both POLEmut and the much more common low-risk NSMP EC., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

The introduction of robotic surgery in hospitals has raised much debate given the various effects on care, costs, education and medical advancement. Purchasing discussions are often approached with more questions than answers and there is a need for reports that provide a case for whether or not such technologies are advantageous from multiple perspectives, and offer insights into ways such devices can be introduced into a hospital setting. This report provides an evidence-based review of a university-affiliated tertiary care hospital's 12-year experience with robotic surgery in gynecologic oncology and delves into the various takeaways and challenges of implementing robotic surgery. Key findings were that robotic surgery significantly reduced complication rates, lengths of hospital stays for patients and overall hospital costs. Key obstacles were large upfront costs and the need for significant leadership and collaboration. Ongoing challenges to evaluating robotics include assessing long-term survival data, making comparisons with concurrently changing hospital conditions and determining how data can be generalized to other departments and institutions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objective: We aimed to evaluate the surgical and oncological outcomes of elderly patients with intermediate to high-risk endometrial cancer undergoing staging with sentinel lymph node (SLN) sampling and pelvic lymphadenectomy., Methods: We conducted a retrospective study of elderly (>65-year-old) patients diagnosed with endometrial cancer between December 2007 and August 2017. These patients had been treated at a single center in Montreal, Canada. We compared the surgical and oncological outcomes of three cohorts undergoing surgical staging in non-overlapping eras: 1) lymphadenectomy, 2) lymphadenectomy and SLN sampling, 3) SLN sampling alone. Using life tables, Kaplan-Meier survival curves and log-rank tests, we analyzed 2-year progression-free survival, overall survival, and disease-specific survival., Results: Our study included 278 patients with a median age of 73 years (range; 65-91): 84 (30.2%) underwent lymphadenectomy, 120 (43.2%) underwent SLN sampling with lymphadenectomy, and 74 (26.6%) had SLN sampling alone. The SLN sampling alone group had shorter operative times with a median duration of 199 minutes (range, 75-393) compared with 231 (range, 125-403) and 229 (range, 151-440) minutes in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts; respectively (p<0.001). The SLN sampling alone group also had lower estimated blood loss with a median loss of 20 mL (range, 5-150) vs 25 mL (range, 5-800) and 40 mL (range, 5-400) in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts, respectively (p=0.002). The 2 year overall survival and progression-free survival were not significantly different between the three groups (p=0.45, p=0.51, respectively). On multivariable analysis after adjusting for age, American Society of Anesthesiologists (ASA) score, stage, grade, and lymphovascular space invasion, adding SLN sampling was associated with better overall survival, (HR 0.2, CI [0.1 to 0.6], p=0.006) and progression-free survival (HR 0.5, CI [0.1 to 1.0], p=0.05)., Conclusion: Sentinel lymph node-based surgical staging is feasible and associated with better surgical outcomes and comparable oncological outcomes in elderly patients with intermediate and high - risk endometrial cancer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Objectives: We measured the variation in practice across all aspects of endometrial cancer (EC) management and assessed the potential impact of implementation of molecular classification., Methods: Centers from across Canada provided representative tumor samples and clinical data, including preoperative workup, operative management, hereditary cancer program (HCP) referrals, adjuvant therapy, surveillance and outcomes, for all EC patients diagnosed in 2016. Tumors were classified into the four ProMisE molecular subtypes., Results: A total of 1336 fully evaluable EC patients were identified from 10 tertiary cancer centers (TC; n = 1022) and 19 community centers (CC; n = 314). Variation of surgical practice across TCs was profound (14-100%) for lymphadenectomy (LND) (mean 57% Gr1/2, 82% Gr3) and omental sampling (20% Gr1/2, 79% Gr3). Preoperative CT scans were inconsistently obtained (mean 32% Gr1/2, 51% Gr3) and use of adjuvant chemo or chemoRT in high risk EC ranged from 0-55% and 64-100%, respectively. Molecular subtyping was performed retrospectively and identified 6% POLEmut, 28% MMRd, 48% NSMP and 18% p53abn ECs, and was significantly associated with survival. Within patients retrospectively diagnosed with MMRd EC only 22% had been referred to HCP. Of patients with p53abn EC, LND and omental sampling was not performed in 21% and 23% respectively, and 41% received no chemotherapy. Comparison of management in 2016 with current 2020 ESGO/ESTRO/ESP guidelines identified at least 26 and 95 patients that would have been directed to less or more adjuvant therapy, respectively (10% of cohort)., Conclusion: Molecular classification has the potential to mitigate the profound variation in practice demonstrated in current EC care, enabling reproducible risk assessment, guiding treatment and reducing health care disparities., Competing Interests: Declaration of Competing Interest Dr. M McConechy, and R Aguirre- Hernandez are employees, and Dr. Huntsman is a founder and Chief Medical Officer of Canexia Health., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the recent trends, acceptability, and effectiveness of digital maternal patient education through summarizing the literature., Methods: Articles published in 2010-2020 on patient education, digital tools, and maternal health were searched on PubMed. Abstract and full texts were reviewed to identify eligible studies and extract key information., Results: Digital patient education studies covered various topics throughout pregnancy, with the greatest number of studies targeting the prenatal period. Among the 55 studies, 38 (69%) reported significant patient outcomes, with the main benefits of increased knowledge (83.3%), emotional benefits (73.7%), and behavioral changes (60.6%). The number of studies per year increased steadily over the past decade, with frequently utilized formats of texts with images (40%), SMS (30.9%), and videos (25.5%). Video produced the highest rate of positive patient outcomes; however, no statistical significance was found., Conclusion: Our study presented evidence supporting the high effectiveness and prevalence of digital tools in maternal patient education, and analyzed the content, platforms, and formats utilized by digital tools of the past decade., Practice Implications: Digital tools are effective and feasible in conducting maternal patient education. No specific patient education format is found to be superior in improving patient's health outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

BRCA1 and BRCA2 are multi-functional proteins and key factors for maintaining genomic stability through their roles in DNA double strand break repair by homologous recombination, rescuing stalled or damaged DNA replication forks, and regulation of cell cycle DNA damage checkpoints. Impairment of any of these critical roles results in genomic instability, a phenotypic hallmark of many cancers including breast and epithelial ovarian carcinomas (EOC). Damaging, usually loss of function germline and somatic variants in BRCA1 and BRCA2, are important drivers of the development, progression, and management of high-grade serous tubo-ovarian carcinoma (HGSOC). However, mutations in these genes render patients particularly sensitive to platinum-based chemotherapy, and to the more innovative targeted therapies with poly-(ADP-ribose) polymerase inhibitors (PARPis) that are targeted to BRCA1/BRCA2 mutation carriers. Here, we reviewed the literature on the responsiveness of BRCA1/2-associated HGSOC to platinum-based chemotherapy and PARPis, and propose mechanisms underlying the frequent development of resistance to these therapeutic agents., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We compared clinical performance of p16/Ki-67 dual-stained cytology and human papillomavirus (HPV) genotyping, via different algorithms-alone, or in combination with cytology-to identify cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) in women referred to as colposcopy. We included 492 cervical specimens (134 normal, 130 CIN1, 99 CIN2, 121 CIN3, 8 cancers) randomly selected from 1158 specimens with valid conventional cytology, HPV (cobas 4800 HPV test) and biopsy results. Dual-stained cytology was retrospectively performed (CINtec PLUS assay) on PreservCyt material; slides were read by a cytologist and confirmed by two pathologists, blinded to cytology, biopsy and genotyping results. Sensitivity and specificity (95% confidence intervals in parentheses) of dual-stained cytology to detect CIN2+ and CIN3+ were compared to other screening tests available for the same women. Positivity rate for dual-stained cytology increased with histological severity: 30.6% in normal, 41.5% in CIN1, 72.7% in CIN2, 86.8% in CIN3 and 87.5% in cancer. Dual-stained cytology alone had lower sensitivity than HPV testing for CIN2+ [80.7% (75.0-85.6) vs 89.9% (85.3-93.5)] and CIN3+ [86.8% (79.7-92.1) vs 92.3% (86.2-96.2)]. However, corresponding specificity values were higher [64.0% (57.9-69.8) vs 56.1% (49.8-62.1) for CIN2+; 54.0% (48.7-59.2) vs 44.4% (39.2-49.6) for CIN3+]. Combining dual-stained cytology with an ASC-US abnormality threshold decreased specificity to 31.4% (25.9-37.4) for CIN2+ and 24.2% (19.9-29.0) for CIN3+. The corresponding values considering low squamous intraepithelial lesion threshold values were 42.8% (36.8-49.0) and 35.0% (30.1-40.1). Dual-stained cytology and HPV testing exhibited similar performance, although the former improved the specificity by 7.9% and 9.6% for CIN2+ and CIN3+, respectively., (© 2020 Union for International Cancer Control.)

Objective: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes., Methods: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method., Results: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11)., Conclusions: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

DNA methylation analysis may improve risk stratification in cervical screening. We used a pan-epigenomic approach to identify new methylation markers along the continuum of cervical intraepithelial neoplasia (CIN) to cervical cancer. Physician-collected samples (54 normal, 50 CIN1, 40 CIN2 and 42 CIN3) were randomly selected from women at a single-center colposcopy clinic. Extracted DNA was subjected to Illumina Infinium EPIC array analysis, and methylation was assessed blinded to histopathological and clinical data. CpG sites whose state of methylation correlated with lesion grade were assessed (Spearman correlation), and a weighted methylation score was calculated comparing normal to CIN3. Validation of the top selected genes was performed in an independent cohort (100 normal, 50 CIN1, 50 CIN2, 50 CIN3 and 8 cervical cancers) of new patients, referred for colposcopic examination at three hospitals, using targeted DNA methylation Illumina amplicon sequencing. The relationship between a combined weighted marker score and progression from normal through precancerous lesions and cervical cancer was compared using one-way ANOVA. Our analyses revealed 7,715 CpGs whose methylation level correlated with progression (from normal to CIN1, CIN2 and CIN3), with a significant trend of increased methylation with lesion grade. We shortlisted a bigenic (hyaluronan synthase 1, HAS1 and ATPase phospholipid transporting 10A, ATP10A corresponding to cg03419058 and cg13944175 sites) marker set; r = 0.55, p < 0.0001. Validation of the four most discriminating genes (CA10, DPP10, FMN2 and HAS1) showed a significant correlation between methylation levels and disease progression (p-value < 2.2 × 10 -16 , adjusted R 2 = 0.952). Translational research of the identified genes to future clinical applications is warranted., (© 2020 UICC.)

Background: Carriers of pathogenic variants in both BRCA1 and BRCA2 genes as a double mutation (BRCA1/2 DM) have been rarely reported in women with epithelial ovarian cancer (EOC)., Methods: We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 EOC patients carrying germline BRCA1/2 DM were compared to high-grade serous EOC women of the COEUR cohort with known germline BRCA1/BRCA2 mutation carrier status (n = 376 non-carriers, n = 65 BRCA1 and n = 38 BRCA2). Clinicopathological parameters evaluated were age at diagnosis, stage of disease, loss of heterozygosity, type of mutation, immunohistochemistry profile, progression occurrence and survival., Results: Median age at diagnosis of BRCA1/2 DM patients was 51.9 years, similar to BRCA1 mutation carriers (49.7 years, p = .58) and younger than BRCA2 mutation carriers (58.1 years, p = .02). Most patients were diagnosed at advanced stage (III-IV; 82%) and were carriers of founder/frequent mutations (69%). Tissue immunostainings revealed no progesterone receptor expression and low intraepithelial inflammation. The 5-year survival rate (60%) was significantly lower than that of BRCA2 mutation carriers (76%, p = .03) but not of BRCA1 mutation carriers (51%, p = .37)., Conclusions: Our data suggests some co-dominant effect of both mutations but the outcome of these patients more closely resembled that of BRCA1 mutation carriers with poor prognosis factors., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: With the rapid uptake of robotic surgery in surgical oncology, its use in the treatment of epithelial ovarian cancers is being evaluated. Complete cytoreduction represents the goal of surgery either at primary cytoreduction or after neoadjuvant chemotherapy in the setting of interval cytoreduction. In selected patients, the extent of disease would enable minimally invasive surgery. The objective of this study was to evaluate the impact of introducing robotic surgery for interval cytoreduction of selected patients with stage III-IV ovarian cancer., Methods: All patients who underwent surgery from November 2008 to 2014 (concurrent time period when robotic and open surgery were used simultaneously) after receiving neoadjuvant chemotherapy for advanced ovarian cancer (stage III-IV) were compared with all consecutive patients who underwent cytoreductive surgery by laparotomy after neoadjuvant chemotherapy between January 2006 and November 2008. Inclusion criteria included an interval cytoreductive surgery by laparotomy or robotic assistance for stage III-IV non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Exclusion criteria included patients treated concurrently for a non-gynecologic cancer, as well as secondary cytoreductive surgeries and diagnostic surgeries without an attempt at tumor reduction. Overall survival, progression-free survival, and peri-operative outcomes were compared for the entire patient cohort with those with advanced ovarian cancer who received neoadjuvant chemotherapy immediately before and after the introduction of robotic surgery., Results: A total of 91 patients were selected to undergo interval cytoreduction either via robotic surgery (n=57) or laparotomy (n=34) after the administration of neoadjuvant chemotherapy. The median age of the cohort was 65 years (range 24-88), 78% had stage III disease, and the median follow-up time was 37 months (5.6-91.4 months). The median survival was 42.8±3.1 months in the period where both robotic surgery and laparotomy were offered compared with 37.9±9.8 months in the time period preceding when only laparotomy was performed (p=0.6). All patients selected to undergo interval robotic cytoreduction following neoadjuvant chemotherapy had a reduction of cancer antigen 125 by at least 80%, resolution of ascites, and CT findings suggesting the potential to achieve optimal interval cytoreduction. All these patients achieved optimal cytoreduction with <1 cm residual disease, including 82% with no residual disease. The median blood loss was 100 mL (mean 135 mL, range 10-1250 mL), and the median hospital stay was 1 day., Conclusion: Robotic interval cytoreductive surgery is feasible in well-selected patients. Future studies should aim to define ideal patients for minimally invasive cytoreductive surgery., Competing Interests: Competing interests: WG and SL obtained partial travel support for proctoring robotic surgery., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objective: To compare the use of robotic radical hysterectomy (RRH) and abdominal radical hysterectomy (ARH) in the United States, with secondary outcomes of perioperative complications, hospital length of stay (LOS), immediate postoperative mortality, cost and a subanalysis compared with laparoscopic radical hysterectomy (LRH)., Design: Retrospective cohort study (Canadian Task Force classification II-2)., Setting: Data from the National Inpatient Sample (NIS), a government-funded database of hospitalization in the United States., Patients and Interventions: All women with cervical cancer undergoing RH between 2008 and 2015 in the United States and included in the NIS database., Measurements and Main Results: Trends in surgical modality, baseline characteristics, LOS, perioperative outcomes, mortality, and hospital charges were compared between RRH and ARH. Regression models were adjusted for baseline characteristics. Among 41,317 women with cervical cancer, 3563 underwent RH, including 21.0% with a robotic procedure, 6.5% with a laparoscopic procedure, and 72.5% with open surgery. The annual rates of ARH declined significantly over the study period, whereas those of RRH increased. Baseline characteristics were comparable between the RRH and ARH groups. Compared with the ARH group, women undergoing RRH had a lower rate of cumulative postoperative complications (18.16% vs 21.21%; odds ratio [OR], 0.81; 95% confidence interval [CI], 0.6-1.0; p = .05), including lower rates of wound infection (0.27% vs 1.82%; OR, 0.14; 95% CI, 0.03-0.6; p < .01), sepsis (0.27% vs 1.20%; OR, 0.22; 95% CI, 0.05-0.9; p = .03), fever (1.87% vs 4.06%; OR, 0.44, 95% CI, 0.3-0.8; p < .01), and ileus (2.8% vs 9.13%; OR, 0.28; 95% CI, 0.12-0.4; p < .01). The LOS was significantly shorter in the RRH group (median, 2 days vs 4 days; p < .01). The total median hospitalization charge was $47,218 for the RRH group, compared with $38,877 for the ARH group (p < .01)., Conclusion: RRH is being increasingly performed in the United States and is associated with shorter LOS and less postoperative morbidity; however, long-term oncologic outcomes require additional attention., (Copyright © 2018 AAGL. Published by Elsevier Inc. All rights reserved.)

There is an absence of information on how physicians make surgical decisions, and on the effect of gender on the processing of information. A novel web based decision-matrix software was designed to trace experimentally the process of decision making in medical situations. The scenarios included a crisis and non-crisis simulation for endometrial cancer surgery. Gynecologic oncologists, fellows, and residents (42 male and 42 female) in Canada participated in this experiment. Overall, male physicians used more heuristics, whereas female physicians were more comprehensive in accessing clinical information (p < 0.03), utilized alternative-based acquisition processes in the non-crisis scenario (p = 0.01), were less likely to consider procedure-related costs (p = 0.04), and overall allocated more time to evaluate the information (p < 0.01). Further experiments leading to a better understanding of the cognitive processes involved in medical decision making could influence education and training and impact on patient outcome.

Background: There is a paucity of empirical evidence to inform the age at which to stop cervical cancer screening. The recommended age to stop screening generally varies between age 50-70 years worldwide. However, cervical cancer incidence and mortality remain high in older women. We used a Markov model of cervical cancer screening to estimate the remaining lifetime risk of cervical cancer at different ages and with different exit screening tests, with the aim of informing recommendations of the age at which to stop cervical cancer screening in developed countries., Methods: For this modelling study, we developed a state transition (Markov) model of cervical cancer natural history and screening. We developed, calibrated, and validated our model using Canadian provincial registries and survey data. To simulate an age-structured population in the model, a new cohort of 236 564 women (one fifth of the population of Canadian women aged 20-24 years in 2012) entered the model every year and were successively modelled in parallel. Successive cohorts entered the model at age 10 years, creating an age-structured population of women aged 10-100 years. Women who had a total hysterectomy were excluded from the analyses. We calibrated our model to human papillomavirus (HPV) infection and cancer incidence with data from Statistics Canada, which compiles the data from 13 individual provincial registries. We chose a three-stage progressive cervical intraepithelial neoplasia model to include differences in management and treatment decisions depending on lesion severity. We modelled infections with four high-risk HPV groups: HPV16 and HPV18; HPV31, HPV33, HPV45, HPV52, and HPV58; HPV35, HPV39, HPV51, HPV56, HPV59, HPV66, and HPV68; and a generic group of other potentially oncogenic HPVs. We estimated 5-year, 10-year, and remaining lifetime risk of cervical cancer for older, unvaccinated women who stopped screening at different ages and underwent different screening tests., Findings: Cervical cancer incidence excluding women with hysterectomies underestimated the incidence of cervical cancer in women with a cervix by up to 71% in women aged 80-84 years. Our model predicted that women without HPV vaccination who have been never screened have a 1 in 45 (95% percentile interval 1 in 32 to 1 in 64) lifetime risk of cervical cancer. Perfect adherence (100% of women screened) to cytology screening every 3 years between the ages of 25 years and 69 years could reduce the lifetime risk of cervical cancer to 1 in 532 women (95% percentile interval 1 in 375 to 1 in 820) without HPV vaccination. Increasing the age at which women stopped cytology screening from 55 years to 75 years led to incremental decreases in cancer risk later in life. A 70-year old woman whose screening history was unknown had an average remaining lifetime risk of 1 in 588 (<1%; 95% percentile interval 1 in 451 to 1 in 873) if she stopped screening. Her remaining lifetime risk at age 70 years was reduced to 1 in 1206 (2·0 times reduction; 95% percentile interval 1 in 942 to 1 in 1748) if she had a negative cytology test, 1 in 6525 (12·9 times reduction; 95% percentile interval 1 in 3167 to 1 in 18 664) if she had a negative HPV test, and 1 in 9550 (18·1 times reduction; 95% percentile interval 1 in 4928 to 1 in 23 228) if she had a negative co-test for cytology and HPV., Interpretation: Cervical cancer risk reductions might be achieved by screening with cytology up to age 75 years, although with diminishing returns. A negative exit oncogenic HPV test or negative HPV test plus cytology correlates with a low remaining lifetime cervical cancer risk for unvaccinated women with a cervix after the age of 55 years., Funding: Canadian Institutes of Health Research., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: We compared the self-sampling performance of the newly designed HerSwab™ device with a physician-collected cervical sample and another self-sample using the cobas® PCR Female swab for the detection of cervical intraepithelial neoplasia (CIN) and cancer., Methods: Women referred for colposcopy at McGill University affiliated hospital clinics collected two consecutive self-samples, one with HerSwab™ and one with cobas® swab, after receiving instructions. The order of sampling was randomized. The colposcopist then collected a cervical sample and conducted a colposcopic examination. Samples were tested for human papillomavirus (HPV) DNA. Sensitivity and specificity to detect CIN2+ and respective 95% confidence intervals (CI) were calculated to compare sampling approaches. The HPV testing agreement between samples was measured using the Kappa statistic., Results: Of 1217 women enrolled, 1076 had complete results for HPV and cytology; 148 (13.8%) had CIN1, 147 (13.7%) had CIN2/3, and 5 (0.5%) had cancer. There was very good agreement between methods for HPV detection (HerSwab™ versus physician: kappa=0.84; cobas® swabs versus physician: kappa=0.81; HerSwab™ versus cobas® swabs: kappa=0.87). The sensitivity of HPV detection for CIN2+ was 87.6% (95%CI: 79.8-93.2) with self-sampling using HerSwab™, 88.6% (95%CI: 80.9-94.0) with self-sampling using the cobas® swab, and 92.4% (95%CI: 85.5-96.7) with physician sampling. Corresponding estimates of specificity were 58.1% (95%CI: 54.1-62.1), 55.0% (95%CI: 50.9-59.0) and 58.7% (95%CI: 54.6-62.6). Cytology (ASC-US or more severe) done on the physician-collected specimen was 80.2% (95%CI: 70.8-87.6) sensitive and 61.4% (95%CI: 57.2-65.5) specific for CIN2+., Conclusions: The HerSwab™ had good agreement with physician sampling in detecting HPV, and adequate performance in detecting high-grade lesions among women referred to colposcopy for abnormal cytology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: To evaluate the anatomical location of sentinel lymph nodes (SLN) following intra-operative cervical injection in endometrial cancer., Methods: All consecutive patients with endometrial cancer undergoing sentinel lymph node mapping were included in this prospective study following intra-operative cervical injection of tracers. Areas of SLN detection distribution were mapped., Results: Among 436 patients undergoing SLN mapping, there were 1095 SLNs removed, and 7.9% of these SLNs found in 13.1% of patients, were detected in areas not routinely harvested during a standard lymph node dissection. These included the internal iliac vein, parametrial, and pre-sacral areas. The SLN was the only positive node in 46.1% (15/36) of cases with successful mapping and completion lymphadenectomy, including 3 cases where the sentinel node in the atypical location was the only node with metastatic disease., Conclusion: SLN mapping using intra-operative cervical injection is capable to map out areas not typically included in a standard lymphadenectomy. The sentinel node is the most relevant lymph node to analyze and may enable to discover metastatic disease in unusual areas., (Copyright © 2017 Elsevier Inc. All rights reserved.)