Publications by authors named "Danielle Vicus"

44 Publications

Factors associated with an increased risk of recurrence in patients diagnosed with high-grade endometrial cancer undergoing minimally invasive surgery: A study of the society of gynecologic oncology (GOC) community of practice (CoP).

Gynecol Oncol 2021 Jun 25. Epub 2021 Jun 25.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of British Columbia, British Columbia, Canada.

Background: Minimally invasive surgery (MIS) is a standard surgical approach for comprehensive surgical staging in women with endometrial cancer. As rates and complexity of MIS are steadily increasing, it is important to identify potential risk factors which may be associated with this approach. This study evaluates the impact of local factors on the risk of disease recurrence.

Methods: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) who underwent MIS between 2012 and 2016 at eight Canadian centers. Data was collected from medical records. The 75th percentile was calculated for estimated uterine volume and weight. All recurrences were categorized into two groups; intra-abdominal vs. extra-abdominal. To search for significant covariates associated with recurrence-free survival a Cox proportional hazard model was performed.

Results: A total of 758 patients were included in the study. Intra-uterine manipulator was used in 497 (35.8%) of patients. Vaginal lacerations were documented in 9.1%. Median follow-up was 30.5 months (interquartile range 20-47). There were 157 who had disease recurrence (20.71%), including 92 (12.14%) intra-abdominal and 60 (7.92%) extra-abdominal only recurrences. In univariate analysis myometrial invasion, LVI, stage, uterine volume and weight > 75th percentile and chemotherapy were associated with increased risk of intra-abdominal recurrence. In multivariable analysis only stage, and specimen weight > 75th percentile (OR 2.207, CI 1.123-4.337) remained significant. Uterine volume, and weight were not associated with increased risk of extra-abdominal recurrences.

Conclusion: For patients diagnosed with HGEC undergoing MIS, extracting a large uterus is associated with a significantly increased risk for intra-abdominal recurrence.
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http://dx.doi.org/10.1016/j.ygyno.2021.06.013DOI Listing
June 2021

Maximizing cancer prevention through genetic navigation for Lynch syndrome detection in women with newly diagnosed endometrial and nonserous/nonmucinous epithelial ovarian cancer.

Cancer 2021 May 13. Epub 2021 May 13.

Division of Gynecologic Oncology, Princess Margaret Cancer Centre/University Health Network/Sinai Health Systems, Toronto, Ontario, Canada.

Background: Despite recommendations for reflex immunohistochemistry (IHC) for mismatch repair (MMR) proteins to identify Lynch syndrome (LS), the uptake of genetic assessment by those who meet referral criteria is low. The authors implemented a comprehensive genetic navigation program to increase the uptake of genetic testing for LS in patients with endometrial cancer (EC) or nonserous/nonmucinous ovarian cancer (OC).

Methods: Participants with newly diagnosed EC or OC were prospectively recruited from 3 cancer centers in Ontario, Canada. Family history questionnaires were used to assess LS-specific family history. Reflex IHC for MMR proteins was performed with the inclusion of clinical directives in pathology reports. A trained genetic navigator initiated a genetic referral on behalf of the treating physician and facilitated genetic referrals to the closest genetics center.

Results: A total of 841 participants (642 with EC, 172 with OC, and 27 with synchronous EC/OC) consented to the study; 194 (23%) were MMR-deficient by IHC. Overall, 170 women (20%) were eligible for a genetic assessment for LS: 35 on the basis of their family history alone, 24 on the basis of their family history and IHC, 82 on the basis of IHC alone, and 29 on the basis of clinical discretion. After adjustments for participants who died (n = 6), 149 of 164 patients (91%) completed a genetic assessment, and 111 were offered and completed genetic testing. Thirty-four women (4.0% of the total cohort and 30.6% of those with genetic testing) were diagnosed with LS: 5 with mutL homolog 1 (MLH1), 9 with mutS homolog 2 (MSH2), 15 with mutS homolog 6 (MSH6), and 5 with PMS2.

Conclusions: The introduction of a navigated genetic program resulted in a high rate of genetic assessment (>90%) in patients with gynecologic cancer at risk for LS.
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http://dx.doi.org/10.1002/cncr.33625DOI Listing
May 2021

Cervical conization and lymph node assessment for early stage low-risk cervical cancer.

Int J Gynecol Cancer 2021 Mar;31(3):447-451

Gynecologic Oncology, Odette Cancer Centre, Toronto, Ontario, Canada

Objective: There has been a contemporary shift in clinical practice towards tailoring treatment in patients with early cervical cancer and low-risk features to non-radical surgery. The objective of this study was to evaluate the oncologic, fertility, and obstetric outcomes after cervical conization and sentinel lymph node (SLN) biopsy in patients with early stage low-risk cervical cancer.

Methods: We conducted a retrospective review in patients with early cervical cancer treated with cervical conization and lymph node assessment between November 2008 and February 2020. Eligibility criteria included patients with a histologic diagnosis of invasive squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage IA1 with positive lymphovascular space invasion (LVSI), stage IA2, or stage IB1 (≤2 cm) with less than two-thirds (<10 mm) cervical stromal invasion.

Results: A total of 44 patients were included in the analysis. The median age was 31 years (range 19-61) and 20 patients (45%) were nulliparous. One patient had a 25 mm tumor while the remaining patients had tumors smaller than 20 mm. Eighteen (41%) patients had LVSI. Median follow-up was 44 months (range 6-137). A total of 17 (39%) patients had negative margins on the diagnostic excisional procedure, and none had residual disease on the repeat cone biopsy. Three (6.8%) patients had micrometastases detected in the SLNs and underwent ipsilateral lymphadenectomy; all remaining non-SLN lymph nodes were negative. Six (13.6%) patients required more definitive surgical or adjuvant treatment due to high-risk pathologic features. There were no recurrences documented. Three patients developed cervical stenosis. The live birth rate was 85% and 16 (94%) of 17 patients had live births at term.

Conclusion: Cervical conization with SLN biopsy appears to be a safe treatment option in selected patients with early cervical cancer. Future results of prospective trials may shed definitive light on fertility-sparing options in this group of patients.
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http://dx.doi.org/10.1136/ijgc-2020-001785DOI Listing
March 2021

Understanding the clinical implication of mismatch repair deficiency in endometrioid endometrial cancer through a prospective study.

Gynecol Oncol 2021 Apr 19;161(1):221-227. Epub 2021 Jan 19.

Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network/Sinai Health Systems, Toronto, Ontario, Canada; Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Canada; Zane Cohen Centre for Digestive Diseases, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address:

Objectives: Findings on impact of mismatch repair deficiency (MMRd) on patient outcomes in endometrial cancer (EC) have been inconsistent to date. The objective of this study was to compare the oncologic outcomes and recurrence patterns between MMRd and MMR-intact (MMRi) endometrioid EC (EEC).

Methods: Between 2015 and 2018, we prospectively recruited 492 EEC cases from three cancer centers in Ontario, Canada. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry (IHC). Clinicopathological, survival and recurrence patterns were compared between MMRd and MMRi cases.

Results: Of 492 EEC, 348 were MMRi (71%) and 144 were MMRd (29%) with median follow-up of 16.8 months (0-69.6). MMRd tumors tended to be grade 2 or 3 (56% vs. 29%, p < 0.001), with propensity for lymphovascular space invasion (28% vs. 18%, p = 0.024), lymph node involvement (7% vs. 5%, p < 0.001) and received more adjuvant treatment (46% vs. 33%, p = 0.027). This group also had significantly lower 3-year recurrence-free survival (78% vs. 90%, p = 0.014) although there was no difference in OS (p = 0.603). MMRd cases were more likely to recur in retroperitoneal lymph nodes (p = 0.045). Upon subgroup analysis, MLH1 methylated tumors had the worst prognostic features and survival outcomes.

Conclusions: MLH1 methylated EECs exhibit more aggressive features compared to other MMRd and MMRi EECs. This may indicate an inherent difference in tumor biology, suggesting the importance of individualized management based on EC molecular phenotype.
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http://dx.doi.org/10.1016/j.ygyno.2021.01.002DOI Listing
April 2021

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

Int J Gynecol Cancer 2021 Apr 18;31(4):545-552. Epub 2020 Dec 18.

Gynecologic Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1136/ijgc-2020-001946DOI Listing
April 2021

Assessment of Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging.

JAMA Surg 2021 Feb;156(2):157-164

Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1001/jamasurg.2020.5060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658802PMC
February 2021

Tumor site discordance in mismatch repair deficiency in synchronous endometrial and ovarian cancers.

Int J Gynecol Cancer 2020 12 20;30(12):1951-1958. Epub 2020 Oct 20.

Gynecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada

Objectives: For synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests.

Methods: 30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing.

Results: Of 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with a pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium.

Conclusions: There was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.
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http://dx.doi.org/10.1136/ijgc-2020-001927DOI Listing
December 2020

Survival after minimally invasive surgery in early cervical cancer: is the intra-uterine manipulator to blame?

Int J Gynecol Cancer 2020 12 9;30(12):1864-1870. Epub 2020 Oct 9.

Gynecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada

Objectives: Minimally 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.

Methods: A 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.

Results: A 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/m (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 (p<0.001), positive lymphovascular space invasion (p=0.02), positive margins (p=0.008), and positive lymph node metastasis (p=0.003). Recurrence-free survival at 5 years was 80% in the no intra-uterine manipulator group and 94% in the intra-uterine manipulator group. After controlling for the presence of residual cancer at hysterectomy, tumor size and high-risk pathologic criteria (positive margins, parametria or lymph nodes), the use of an intra-uterine manipulator was no longer significantly associated with worse recurrence-free survival (HR 0.4, 95% CI 0.2 to 1.0, p=0.05). The only factor which was consistently associated with recurrence-free survival was tumor size (HR 2.1, 95% CI 1.5 to 3.0, for every 10 mm increase, p<0.001).

Conclusion: After 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.
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http://dx.doi.org/10.1136/ijgc-2020-001816DOI Listing
December 2020

Cytology-based screening for anal intraepithelial neoplasia in women with a history of cervical intraepithelial neoplasia or cancer.

Cancer Cytopathol 2021 02 1;129(2):140-147. Epub 2020 Oct 1.

Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: High-risk human papillomavirus (HPV) has been identified in the pathogenesis of anal cancer. The purpose of this study was to assess the prevalence of abnormal anal cytology and HPV in women aged ≥40 years who have a history of high-grade cervical squamous intraepithelial lesion (SIL) or cancer and to estimate the prevalence of anal intraepithelial neoplasia (AIN) using cytology as the primary screening modality.

Methods: Women who had a history of high-grade cervical SIL or cancer and were ≥40 years of age were included in this prospective study. Anal cytology with HPV-DNA testing was performed. All patients with abnormal anal cytology were referred for high-resolution anoscopy (HRA), and abnormal lesions were biopsied and treated if pathologically confirmed. Abnormal anal cytology correlated with HPV status, HRA findings, and clinical and demographic characteristics.

Results: A total of 317 women completed the study. Of these, 96 (30.3%) had abnormal anal cytology (high-grade SIL, 12.5%; low-grade SIL, 19.8%; atypical squamous cells, cannot exclude high-grade SIL, 6.3%; atypical squamous cells of undetermined significance, 61.5%) and 101 (31.9%) were HPV-DNA-positive. There was a significant association between abnormal cytology results and the presence of high-risk HPV. Of the 96 patients with abnormal cytology, 30 (31.3%) had biopsy-proven AIN on HRA, representing 9.5% of the total patient cohort; of these, 10 (33.3%) had low-grade AIN and 20 (66.7%) had high-grade AIN. Older age and smoking were significant risk factors for abnormal anal cytology.

Conclusion: Women aged ≥40 years with a history of high-grade cervical SIL or cancer have a high rate of AIN. Screening for anal cancer may therefore be considered in this patient population. The optimal screening approach should be addressed in future studies.
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http://dx.doi.org/10.1002/cncy.22360DOI Listing
February 2021

Outcomes after the regionalization of care for high-grade endometrial cancers: a population-based study.

Am J Obstet Gynecol 2021 03 12;224(3):274.e1-274.e10. Epub 2020 Sep 12.

Division of Gynecologic Oncology, Odette Cancer Center, Department of Obstetrics and Gynaecology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Background: In June 2013, Ontario Health (Cancer Care Ontario), the agency responsible for advancing cancer care in Ontario, Canada, published practice guidelines recommending that gynecologic oncologists at tertiary care centers manage the treatment of patients with high-grade endometrial cancers. This study examines the effects of this regionalization of care on patient outcomes.

Objective: This study aimed to evaluate the impact of the regionalization of surgery for high-grade endometrial cancer on patient and treatment outcomes.

Study Design: In this retrospective cohort study, patients diagnosed with nonendometrioid high-grade endometrial cancer from 2003 to 2017 were identified using province-wide administrative databases. To allow 6 months for knowledge translation, 2 periods were defined, with January 1, 2014, as the cutoff. Methods for segmented regression were used to test the effect of the guidelines. Multivariable Cox proportional hazards regression was used to evaluate whether regionalization of care had an impact on patient survival.

Results: There were 3518 patients with nonendometrioid high-grade endometrial cancer identified. The case mix as represented by patient comorbidities and the disease stage distribution did not differ significantly between the 2 regionalization periods. There was a significant increase (69%-85%; P<.001) in the proportion of primary surgeries performed by gynecologic oncologists after regionalization, which was not explained by secular trends. After regionalization, the proportion of patients who had surgical staging (50%-63%; P<.001) and the proportion of patients who received adjuvant treatment (65%-71%; P<.001) increased significantly. After adjusting for age, stage, and comorbidities, there was a decrease in the hazard of mortality (hazard ratio, 0.85 [95% confidence interval, 0.73-0.99]; P=.04) after regionalization.

Conclusion: The publication of a regionalization policy for the treatment of high-grade endometrial cancers in Ontario led to an increase in the proportion of surgeries performed by gynecologic oncologists. This also translated into a significant improvement in patient survival.
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http://dx.doi.org/10.1016/j.ajog.2020.09.012DOI Listing
March 2021

Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer.

Cancer 2020 11 18;126(22):4886-4894. Epub 2020 Aug 18.

Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network, Sinai Health Systems, Toronto, Ontario, Canada.

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 (with MLH1 promoter 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 with MLH1 promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%.

Conclusions: Sequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter 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.
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http://dx.doi.org/10.1002/cncr.33144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693219PMC
November 2020

Uterine rupture: an unusual presentation of a uterine perivascular epithelioid cell tumor (PEComa).

Int J Gynecol Cancer 2020 12 6;30(12):2008-2011. Epub 2020 Aug 6.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Toronto Faculty of Medicine, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1136/ijgc-2020-001837DOI Listing
December 2020

Evaluating the diagnostic performance of preoperative endometrial biopsies in patients diagnosed with high grade endometrial cancer: A study of the Society of Gynecologic Oncology (GOC) Community of Practice (CoP).

Gynecol Oncol 2020 10 19;159(1):52-57. Epub 2020 Jul 19.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Toronto, Canada; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Trillium Health Partners, Canada. Electronic address:

Background: High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies.

Methods: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction.

Results: Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36-4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33-2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52-0.96).

Conclusion: GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed.
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http://dx.doi.org/10.1016/j.ygyno.2020.06.510DOI Listing
October 2020

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

Int J Gynecol Cancer 2020 Jun 22. Epub 2020 Jun 22.

Gynecologic Oncology, Odette Cancer Centre, Toronto, Ontario, Canada

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.
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http://dx.doi.org/10.1136/ijgc-2020-001205DOI Listing
June 2020

The prognostic role of horizontal and circumferential tumor extent in cervical cancer: Implications for the 2019 FIGO staging system.

Gynecol Oncol 2020 08 26;158(2):266-272. Epub 2020 May 26.

Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. Electronic address:

Objective: The FIGO 2019 update on cervical cancer staging removed horizontal tumor extent (HZTE) as a staging variable. Evidence is needed to substantiate this change. The prognostic significance of HZTE and a related variable, circumferential tumor extent (%CTE), is similarly unknown. We aimed to investigate the association of HZTE and %CTE with survival outcomes in cervical cancer patients.

Methods: We identified patients treated with primary surgery for stage I cervical cancer in a single institution during a 9-year period. HZTE and, when available, %CTE were obtained from pathology records. Cases were staged using 2019 FIGO staging. Correlations between HZTE, %CTE and FIGO stage with recurrence-free (RFS) and disease-specific survival (DSS) were determined using univariable and multivariable analyses.

Results: 285 patients were included with a median follow-up of 48 (range 7-123) months. HZTE was statistically associated with RFS and DSS on univariate and multivariate analysis. None of the 168 stage IA patients in our series had tumor recurrence or death during follow-up, including 42 with HZTE ≥7 mm. None of the patients with a tumor horizontal extent <7 mm experienced recurrence or death. %CTE correlated only with RFS on univariate analysis. 2019 FIGO stage did not independently correlate with RFS or DSS in our sample.

Conclusions: HZTE is an independent predictor of survival in cervical carcinoma. In stage IA tumors, however, HZTE does not offer superior prognostic value, supporting the 2019 FIGO recommendations to remove this variable from staging in these cases. HZTE may be useful in larger tumors in which staging depends on maximum tumor size. %CTE is not an independent prognostic variable in cervical cancer, and we advise against its use.
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http://dx.doi.org/10.1016/j.ygyno.2020.05.016DOI Listing
August 2020

Malignant Melanoma of the Vulva and Vagina: A US Population-Based Study of 1863 Patients.

Am J Clin Dermatol 2020 Apr;21(2):285-295

Division of Gynecologic Oncology, Department of Surgical Oncology, University Health Network, Toronto, ON, Canada.

Background: Vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of malignant melanomas with important differences in biology and treatment.

Objective: The objective of this study was to describe the epidemiology and prognosis of VuM and VaM in a large representative cohort.

Methods: Women with invasive VuM or VaM were identified from the Surveillance, Epidemiology and End Results-18 population representing 27.8% of the US population. Data on age, ethnicity, stage, location, histopathology, primary surgery, and lymphadenectomy were collected. The Kaplan-Meier method was used to analyze disease-specific and overall survival. Univariate and multivariate regression models were used to identify factors with a significant association with disease-specific survival.

Results: A total of 1400 VuM and 463 VaM were included for further analysis; 78.6% and 49.7% of women with VuM and VaM underwent surgery, but only 52.9% of women with non-metastatic VuM and 42.9% of women with non-metastatic VaM undergoing surgery had lymph node assessment; one third of these had positive nodes. Superficial spreading was the most common subtype in VuM, and nodular melanoma in VaM (p < 0.001). The median disease-specific survival was 99 months (95% confidence interval 60-138) and 19 months (95% confidence interval 16-22), respectively. Survival was significantly associated with age at diagnosis, ethnicity, stage, surgery, lymph node metastases, histologic subtype, ulceration, mitotic count, and tumor thickness in VuM, and stage, surgery, and lymph node involvement in VaM. In the Cox model, lymph node status and number of mitoses remained independent predictors of outcome in VuM; in VaM, only lymph node status remained significant.

Conclusions: The overall prognosis of VuM and VaM remains poor. The American Joint Committee on Cancer staging system is applicable and should be used for VuM; however, lymph node status and mitotic rate are the most important predictors of survival. Lymph node status should be assessed and patients with positive nodes may be candidates for adjuvant treatment.
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http://dx.doi.org/10.1007/s40257-019-00487-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125071PMC
April 2020

Long term outcomes in patients with sentinel lymph nodes (SLNs) identified by injecting remaining scar after previously excised vulvar cancer.

Gynecol Oncol 2019 10 23;155(1):83-87. Epub 2019 Aug 23.

University of Toronto, Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Background: Lymph node metastasis is the most important prognostic factor in patients with vulvar squamous cell carcinoma (SCC). Previous excision of the vulvar tumor may disrupt lymphatic channels and alter the accuracy of the sentinel lymph node (SLN) biopsy. The purpose of this study was to measure outcomes after SLN biopsy in patients with and without previous excision of the vulvar tumor.

Methods: Retrospective study of patients at a single institution with primary vulvar cancer, clinically negative nodes, and vulvar tumors < 4 cm treated with surgical excision who had SLN biopsy (2008-2015).

Results: There were 106 cases of concomitant wide local excision (WLE) and SLN biopsy and 24 additional cases of patients who had previous vulvar surgery and no visible tumor; these patients underwent scar re-excision and SLN biopsy. Median follow-up was 31 months. Patients who had previous tumor excision were more likely to be of younger age (p = 0.0001), have a smaller tumor (p = 0.002), and less depth of invasion (p = 0.02). In the wide local excision of the scar specimen, 11 patients (46%) had no residual disease left, 8 patients (33%) had only vulvar intraepithelial neoplasia (VINIII), 4 patients (17%) had carcinoma in situ with focal invasion and 1 patient (4%) had invasive carcinoma within the second specimen, resected with clear margins. There were no groin recurrences in patients who underwent scar re-excision and who had a negative SLN biopsy.

Conclusion: SLN biopsy is feasible and safe in patients who have had previous excision of the vulvar tumor and present with a scar. When a SLN is detected by injecting the remaining scar, this accurately reflects the nodal status and does not negatively impact oncologic outcomes.
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http://dx.doi.org/10.1016/j.ygyno.2019.08.015DOI Listing
October 2019

p53, Mismatch Repair Protein, and POLE Abnormalities in Ovarian Clear Cell Carcinoma: An Outcome-based Clinicopathologic Analysis.

Am J Surg Pathol 2019 12;43(12):1591-1599

Departments of Laboratory Medicine and Molecular Diagnostics.

The PROMISE diagnostic algorithm, which uses p53, mismatch repair (MMR) protein immunohistochemistry, and DNA polymerase ε (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<0.05, Fisher exact test). In univariate analysis, abnormal p53 and positive lymph node status had worse DFS, whereas bilaterality, surface involvement, and advanced stage were associated with worse DFS, overall survival and DSS (P<0.05, Cox regression). On multivariate analysis, only stage retained statistical association with survival. Using a molecular-based approach designed for endometrial carcinoma, most ovarian clear cell carcinomas fall into the copy-number-low molecular subgroup. However, a small but important subset has an abnormal p53 expression (copy-number-high group). This subset is associated with adverse features including extrapelvic disease, nodal metastases, and recurrence similar to endometrial and ovarian endometrioid cancer. Thus, testing for this marker has potential prognostic significance. The role of other markers in the PROMISE algorithm remains to be elucidated, as we found a low frequency of MMR abnormalities and no pathogenic POLE mutations in our series.
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http://dx.doi.org/10.1097/PAS.0000000000001328DOI Listing
December 2019

Patterns of recurrence and impact on survival in patients with clear cell ovarian carcinoma.

Int J Gynecol Cancer 2019 09 3;29(7):1164-1169. Epub 2019 Jul 3.

Gynecologic Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Background: Patients with recurrent clear cell ovarian cancer have poor prognosis and limited effective systemic treatment options.

Objectives: To characterize patterns of recurrence and compare overall survival and post-recurrence survival parameters in patients with recurrent ovarian clear cell carcinoma.

Methods: Clinical 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.

Results: A 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.

Conclusion: Ovarian 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.
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http://dx.doi.org/10.1136/ijgc-2019-000287DOI Listing
September 2019

Rates over time and regional variation of radical minimally invasive surgery for cervical cancer: A population based study.

Gynecol Oncol 2019 08 3;154(2):338-344. Epub 2019 Jun 3.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada; Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; ICES, Toronto, ON, Canada. Electronic address:

Objective: Determine rates of radical minimally invasive surgery (MIS) for cervix cancer in Ontario, and whether these rates varied over time and by region. Assess whether changes in the use of MIS impacted length of hospital stay and readmissions.

Methods: Retrospective population-based cohort study of women undergoing radical surgery for cervical cancer between 2002 and 2015. Radical MIS versus laparotomy were compared. Trends in rate of MIS over time, length of hospital stay, and readmission within 30 days were determined. Multivariate logistic regression was used to determine factors associated with MIS approach.

Results: 805 women underwent radical abdominal surgery versus 538 radical minimally invasive surgery. Radical MIS increased over the study period, from 17.7% in 2002 to 61.5% in 2015. The most significant predictor of MIS approach was hospital site, with a 14-fold difference in sites with highest and lowest uptake of MIS. Mean length of hospital stay was significantly shorter after radical MIS compared to radical abdominal surgery (1.1 v. 4.2 days). Hospital readmission within 30 days was reduced over the study period for MIS but remained stable following abdominal surgery.

Conclusions: Although rates of radical MIS increased in Ontario over the time period studied, this seems to have been driven by a few high volume centres. Cervical cancer is rare and it takes time to develop the skills to carry out the procedure effectively. Abandonment of minimally invasive radical hysterectomy may have a significant impact on surgical training and subsequent proficiency in the skills unique to this procedure.
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http://dx.doi.org/10.1016/j.ygyno.2019.05.019DOI Listing
August 2019

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

Gynecol Oncol 2019 03;152(3):480-485

Division of Gynecologic Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ygyno.2018.09.008DOI Listing
March 2019

Sentinel lymph nodes in vulvar cancer: Management dilemmas in patients with positive nodes and larger tumors.

Gynecol Oncol 2019 01 16;152(1):94-100. Epub 2018 Nov 16.

University of Toronto, Department of Obstetrics and Gynecology, Toronto, Ontario, Canada; Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Background: Although sentinel lymph node (SLN) biopsy has been routinely used in the treatment of invasive squamous cell carcinoma (SCC), questions still remain regarding the management of patients with positive nodes, as well as its use in patients with larger tumors.

Methods: Retrospective study of all patients at a single institution with primary vulvar cancer who had SLN biopsy (2008-2015). Patient and tumor characteristics were collected from hospital records. For patients with positive SLN and for those with tumors ≥40 mm, recurrence rates and location were specifically recorded.

Results: SLN biopsy was successful in 159 patients (245 groins). Median follow-up was 31 months. 120 patients (187 groins) had a negative SLN without an inguinofemoral lymph node dissection (IFL); there were 6 ipsilateral groin recurrences (5%). 7 patients had micrometastasis (≤2 mm) in the SLN and were treated by radiotherapy. There were no recurrences in the irradiated groins. 19 patients with a positive unilateral SLN had bilateral IFL. One (5.3%) had a positive node in the contralateral groin. 9 patients with positive unilateral SLN had subsequent ipsilateral IFL; there were no groin recurrences in the contralateral groin. 20 patients had tumor size ≥40 mm. 11 patients had a negative SLN biopsy, and thus no IFL; of these patients, 1 had an isolated groin recurrence (9%).

Conclusion: These data suggest it is reasonable to omit a full groin dissection for micrometastatic disease in the SLN, and to perform a unilateral groin dissection in patients with unilateral SLN metastasis. SLN alone in larger tumors may have a higher groin recurrence rate.
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http://dx.doi.org/10.1016/j.ygyno.2018.10.047DOI Listing
January 2019

Melanoma of the Vulva and Vagina: Surgical Management and Outcomes Based on a Clinicopathologic Reviewof 68 Cases.

J Obstet Gynaecol Can 2019 Jun 2;41(6):762-771. Epub 2018 Nov 2.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON; Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON.

Objective: This study sought to evaluate the clinicopathologic features, surgical management, and survival of patients over 12 years at two academic centres.

Methods: Patients diagnosed with vulvar or vaginal melanoma between 2002 and 2014 were identified through pathology databases. Clinical and pathologic data were extracted from the medical records. The Kaplan-Meier method was used to calculate recurrence-free survival and overall survival (OS), and univariate analyses using a Cox proportional hazard model were used to detect covariates related to survival.

Results: Patients with vulvar melanoma were more likely to undergo surgical excision (84.0% vs. 55.6%, P = 0.0243) and were more likely to achieve negative margins (70.0% vs. 16.7%, P < 0.0001). Forty-eight percent of patients with vulvar melanoma had a lymph node evaluation; sentinel node biopsies were performed in 32%. Actuarial median OS for vulvar melanoma was 45 months compared with 10.48 months for vaginal melanoma. A subset of 10 patients with vulvar melanoma who survived longer than 60 months was identified. Eight significant predictors of OS were demonstrated for vulvar melanomas: clinical stage, maximum tumour size, tumour thickness, lymphovascular space invasion status, clinically enlarged lymph nodes, sentinel lymph nodes, lymph node status, and radiation treatment. Patients with positive or indeterminate margin status demonstrated a higher risk of recurrence than did patients with negative margins (hazard ratio 2.60; 95% CI 1.14-5.90).

Conclusion: Surgical excision with adequate margins is the mainstay of primary management when feasible. Lymph node evaluation, including sentinel nodes, may be considered in selected patients. Vulvar and vaginal sites differ markedly with respect to pathology, initial management, and survival, and they should be evaluated separately.
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http://dx.doi.org/10.1016/j.jogc.2018.07.011DOI Listing
June 2019

FIGO Versus Silverberg Grading Systems in Ovarian Endometrioid Carcinoma: A Comparative Prognostic Analysis.

Am J Surg Pathol 2019 02;43(2):161-167

Departments of Laboratory Medicine.

The International Federation of Obstetrics and Gynecology (FIGO) grading system for endometrial carcinoma is currently applied to ovarian endometrioid carcinoma (OEC) in many practices. However, previous reports claim superior prognostication by using the Silverberg grading system for ovarian carcinoma. Thus, a thorough comparison between FIGO and Silverberg in OEC is still warranted. A total of 72 OECs diagnosed at our institution were independently graded using both systems. Grade (G) following Silverberg was based on combined scores for architecture, nuclear atypia, and mitotic activity. FIGO grading was based on the % of nonsquamous solid component; severe atypia warranted upgrade to the architectural FIGO grade (G1 to G2 or G2 to G3). Case grouping by grade was correlated with disease-free (DFS), disease-specific (DSS), and overall (OS) survival. Eleven (15.3%) OECs were bilateral, 26 (36.1%) had ovarian surface involvement, and 12 (16.7%) had lymphovascular space invasion. Forty-seven OECs were stage I (65%), 16 (22%) stage II, and 9 (13%) stage III. Median follow-up period was 62 months (range: 1 to 179 mo). Median DFS was 60.5 months (1 to 179 mo); median OS was 61 months (1 to 179 mo). Sixteen (22%) OECs recurred and 9 (13%) patiets died of disease. In univariate analysis, both FIGO and Silverberg correlated significantly with DFS, DSS, and OS (all with P<0.05). However, when compared in multivariate analysis, only Silverberg retained statistical correlation with survival (P<0.05). G1+G2 OEC by Silverberg had significantly better DFS, DSS, and OS compared with G3; such separation was not seen with FIGO. Survival was similar in Silverberg G1 and G2 tumors even 5 years after diagnosis, whereas FIGO G2 tumors had survival approaching G1 in the first 5 years, but declined after the 5-year mark approaching G3 tumors. Tumor laterality, lymphovascular space invasion, and stage also correlated with outcome. Stage showed prognostication superior to all other variables in multivariate analysis. As currently defined, the Silverberg grading system is a better predictor of survival than FIGO. Such differences may be explained by the G2 OEC groups, with G2 Silverberg clustering with G1 tumors, and having a more favorable behavior compared with G2 FIGO. Thus, Silverberg may be preferable in order to stratify patients in low and high-risk categories for prognosis and disease management.
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http://dx.doi.org/10.1097/PAS.0000000000001160DOI Listing
February 2019

Laparoscopic ovarian transposition prior to pelvic radiation for gynecologic cancer.

Gynecol Oncol Rep 2018 May 18;24:78-82. Epub 2018 Apr 18.

Division of Gynecologic Oncology, Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.

This study evaluates a novel technique of laparoscopic ovarian transposition performed by Gynecologic Oncologists prior to pelvic radiation for gynecologic cancer. A retrospective review was completed of all patients that underwent laparoscopic ovarian transposition from February 2007 to June 2017 at one tertiary care cancer. The technique involves salpingectomy, followed by retroperitoneal dissection to move the ovaries lateral to the hepatic and splenic flexures of the colon. Normal ovarian function was defined by the absence of vasomotor symptoms, FSH and menstrual history (if menstruating). The radiation dose to the ovary was calculated through dose volume histograms from three-dimensional image planning. Ten patients had laparoscopic ovarian transposition, of which, eight patients received post-operative external beam radiation to the pelvis (45-59.4 Gy). Four had additional brachytherapy (35.5-40 Gy). Median age and follow up were 29 years (18-37), and 20 months (6-103). Nine patients had cervical and one had vaginal cancer. Four patients were treated with primary radiation, three had radical trachelectomy with adjuvant radiation, and three had radical hysterectomy with one of three receiving adjuvant radiation. No patients developed vasomotor symptoms (0/8 (95% CI 0-19%)). FSH was normal in 2/2 patients. Menses continued post-radiation in 5/7 women who retained their uterus. The median radiation dose to the right and left ovary was 0.51 (0.23-1.1) Gy and 0.53 (0.23-1.1) Gy, respectively. Laparoscopic ovarian transposition with mobilization to the hepatic and splenic flexures of the colon achieves preservation of ovarian function in women prior to pelvic radiation.
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http://dx.doi.org/10.1016/j.gore.2018.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003432PMC
May 2018

Feasibility and safety of same-day discharge after laparoscopic radical hysterectomy for cervix cancer.

Gynecol Oncol 2017 12 29;147(3):572-576. Epub 2017 Sep 29.

Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada; Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Objective: To evaluate the safety and feasibility of same day-discharge (SDD) after laparoscopic radical hysterectomy for cervix cancer by determining complication rates and factors associated with post-operative admission.

Methods: In this retrospective cohort study, patients undergoing laparoscopic radical hysterectomy for cervix cancer at a single institution from January 2006 to November 2015 were identified. Admitted patients were compared to same-day discharge patients. Rates of post-operative complications and readmission were analyzed and regression analysis used to determine factors associated with admission.

Results: 119 patients were identified. 75 (63%) were SDD patients (mean stay 156.7±50.2min) and 44 (37%) were admitted patients (mean stay 1.2±0.6days). Ten (13%) SDD patients sought medical attention within 30days post-operatively vs. nine (20%) admitted patients (p=0.17). Reasons SDD patients sought attention included pain (n=1), wound concerns (n=2), vaginal bleeding (n=2), DVT/VTE (n=1), fever (n=2) and fistula (n=2). All patients developed symptoms and presented between 5 and 13days post-operatively thus no complications could have been detected or prevented through initial admission. Four SDD patients were readmitted within 30days of surgery (p=0.25), two required re-operation (p=0.16). Admitted patients were older (p=0.049), had longer operations (p=0.02), increased blood loss (p=0.0004), increased intra-operative complications (p=0.001), surgery later in the day (p=0.004) and before April 2010 (p=0.001). On multivariate analysis, older age (OR1.05, p=0.03), surgery later in the day (OR 7.22, p=0.002) and presence of an intra-operative complication (OR 10.25, p=0.02) were significantly associated with admission.

Conclusion: Same-day discharge after laparoscopic radical hysterectomy for cervix cancer is safe, with a low risk of post-operative morbidity and hospital readmission.
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http://dx.doi.org/10.1016/j.ygyno.2017.09.026DOI Listing
December 2017

Is adjuvant chemotherapy beneficial for surgical stage I ovarian clear cell carcinoma?

Gynecol Oncol 2017 10 29;147(1):54-60. Epub 2017 Jul 29.

Division of Gynecologic Oncology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, University of Toronto, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ygyno.2017.07.128DOI Listing
October 2017

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

Gynecol Oncol 2016 Nov 9;143(2):258-263. Epub 2016 Sep 9.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada; Division of Gynecologic Oncology, Odette Cancer Centre, Toronto, Ontario, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ygyno.2016.09.006DOI Listing
November 2016

Uterine Clear Cell Carcinoma: Does Adjuvant Chemotherapy Improve Outcomes?

Int J Gynecol Cancer 2017 01;27(1):69-76

*Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, †Division of Gynecologic Oncology, Princess Margaret Cancer Centre, ‡Biostatistics Department, University Health Network, §Division of Anatomic Pathology, Sunnybrook Health Sciences Centre, and ∥Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.

Objectives: Women with uterine clear cell carcinoma (UCCC) are at high risk of relapse. Adjuvant chemotherapy (CT) is often recommended, although its effectiveness remains controversial. Our objective was to evaluate treatment-related outcomes of patients with UCCC, particularly those treated with adjuvant CT.

Methods: In this retrospective cohort study, patients diagnosed with UCCC at 2 academic cancer centers from 2000 to 2014 were included. Clinical, surgical, and pathological data were collected. Survival estimates were obtained using the Kaplan-Meier method and compared by log rank test. Multivariable analysis was used to determine the effect of CT and radiation therapy (RT) on overall survival (OS) and progression-free survival (PFS).

Results: We included 146 patients with UCCC, with a median follow-up of 27 months (range, 1-160). Ninety-five (65%) patients presented with stage I to II disease and 51 (35%) with stage III to IV disease. Forty-six percent of patients with clinical stage I were upstaged after surgery: 29% were upstaged to stages III and IV. Thirty-one percent of patients with early-stage disease and 70% with advanced-stage received CT. Among recurrences, the majority had distant relapse in both early-stage (61.5%) and advanced-stage (96.3%) diseases. In both patients with early-stage and advanced-stage diseases, adjuvant CT did not improve OS or PFS. On multivariate analysis, CT was not a significant factor associated with improved PFS (hazard ratio [HR], 1.37; 95% confidence interval [CI], 0.69-2.71; P = 0.37) or OS (HR, 0.58; 95% CI, 0.24-1.38; P = 0.22), whereas RT was associated with improved PFS (HR, 0.51; 95% CI, 0.29-0.90; P = 0.02) and OS (HR, 0.19; 95% CI, 0.09-0.42; P < 0.001).

Conclusions: The high rate of upstaging after surgery highlights the importance of lymph node assessment. The high rate of distant recurrence questions the effectiveness of current CT regimens and warrants the development of novel systemic approaches. The role of adjuvant RT deserves further study.
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http://dx.doi.org/10.1097/IGC.0000000000000839DOI Listing
January 2017

A comparison of the toxicity and tolerability of two intraperitoneal chemotherapy regimens for advanced-stage epithelial ovarian cancer.

Gynecol Oncol 2016 Jan 4;140(1):36-41. Epub 2015 Nov 4.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada; Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada. Electronic address:

Objectives: Randomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC.

Methods: Retrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan-Meier estimate; the log-rank test was used to compare survival curves.

Results: Of the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4 cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs. 1.6%, p=0.033), grade 3 neuropathy (7.8% vs. 0%, p=0.013) and grade 2-3 neutropenia (22.1% vs. 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups.

Conclusion: IP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities.
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http://dx.doi.org/10.1016/j.ygyno.2015.11.005DOI Listing
January 2016
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