Publications by authors named "Lilian T Gien"

49 Publications

Hormone maintenance therapy for women with low-grade serous ovarian cancer in the front-line setting: A systematic review.

Gynecol Oncol 2021 Jul 26. Epub 2021 Jul 26.

Division of Gynecologic Oncology, Trillium Health Partners, Credit Valley Hospital, Mississauga, ON, Canada. Electronic address:

Objective: Low-grade serous ovarian cancer (LGSOC) is a rare form of ovarian cancer that accounts for 5-10% of epithelial ovarian cancers. LGSOCs are difficult to treat as they respond poorly to traditional chemotherapy treatments. This systematic review aims to appraise the literature describing the efficacy of hormone maintenance therapy (HMT) in patients with LGSOC given after cytoreductive surgery.

Methods: Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from inception to November 2020. No language restrictions were applied. Publications describing HMT in the primary setting following cytoreductive surgery with or without chemotherapy in women with LGSOC were included. Publications describing HMT in recurrence, non-LGSOC carcinomas, and in-vitro or animal studies were excluded along with case reports, case series, and conference proceedings. We summarized oncologic outcomes, HMT used, and hormone receptor status where reported. Studies were assessed for risk of bias and quality of evidence.

Results: The literature search identified 14,799 records. Four cohort studies met eligibility criteria. A total of 558 patients were included, of which 127 were treated with HMT. There was significant heterogeneity between studies demonstrated by differences in HMT regimens used, dosing, and study population, leading to various outcomes following treatment with HMT.

Conclusions: Treatment of LGSOC remains a challenge. One retrospective study demonstrated improved progression-free survival following HMT for LGSOC, while two others failed to show significant improvements. However, there is limited data available in the literature which restricts the generalizability of these results. Therefore, well-designed, prospective, and randomized trials are needed to confirm the benefit of HMT in patients with this rare subgroup of ovarian cancer.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.027DOI Listing
July 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

Factors impacting length of stay and survival in patients with advanced gynecologic malignancies and malignant bowel obstruction.

Int J Gynecol Cancer 2021 May 28;31(5):727-732. Epub 2021 Jan 28.

University of Toronto Faculty of Medicine, Toronto, Ontario, Canada

Objectives: Malignant bowel obstruction in patients with gynecologic malignancies can impose a large symptomatic burden. The objectives of this study were to identify factors associated with shorter length of hospital stay and overall survival in gynecologic oncology patients with malignant bowel obstructions.

Methods: A retrospective chart review was performed from December 2014 to March 2019 on patients admitted to a tertiary care center with a malignant bowel obstruction and advanced gynecologic malignancy. Data collection included patient and tumor characteristics, malignant bowel obstruction management (such as conservative management with bowel rest, nasogastric tube, pharmacotherapy or active intervention with surgery, chemotherapy, radiation, total parenteral nutrition or interventional stents), length of hospital stay, and survival outcomes. Statistical analysis included comparisons with Student's t-test and χ test, multivariable analysis, and survival analysis.

Results: A total of 107 patients with gynecologic cancer with malignant bowel obstruction were included. The majority of patients (63%, n=67) had ovarian cancer. The median length of hospital stay was 12 days (range 1-23), with a median overall survival after malignant bowel obstruction diagnosis of 7 months (range 0.1-64.1). Patients with active interventions had a longer length of stay compared with those with conservative management (13 vs 6 days, p<0.001). However, patients who received multiple active interventions had increased overall survival (9.1 vs 2.9 months, p=0.049).

Conclusion: Patients who received multimodal treatment for malignant bowel obstruction had an increased length of stay and improvement in survival of over 6 months. This emphasizes the importance of a multidisciplinary approach to actively manage malignant bowel obstruction in advanced gynecologic cancer.
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http://dx.doi.org/10.1136/ijgc-2020-002133DOI Listing
May 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

Does Radical Hysterectomy for Clinically Apparent Stage II Endometrial Cancer Affect Risk of Local Recurrence?

J Obstet Gynaecol Can 2021 May 4;43(5):564-570. Epub 2021 Jan 4.

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

Objective: Compare recurrence-free survival (RFS) and morbidity between radical hysterectomy (RH) and simple hysterectomy (SH) for clinically diagnosed stage II endometrial cancer.

Methods: A multicentre, retrospective study, from 2000 to 2015, involving patients with endometrial cancer with cervical involvement preoperatively and stromal invasion on final pathology. Wilcoxon rank-sum test, Fisher exact test, Kaplan-Meier survival functions, and Cox proportional hazards models were used for analysis.

Results: Ninety of 1613 patients had clinical stage II endometrial cancer; 57 underwent RH and 33 underwent SH, with no difference in adjuvant treatment or morbidity. About half of patients (51%) had pathologic stage III-IV disease. Mean follow-up was 3.3 and 3.8 years for SH and RH, respectively. Thirty-three percent of patients with RH and SH experienced a recurrence. Most recurrences were distant: 90% with SH and 79% with RH. There was no difference in RFS between groups (2-year: SH 65% vs. RH 75%; 5-year: SH 54% vs. RH 63%; P = 0.72). Controlling for stage, adjuvant treatment, and margin status, RH was not associated with RFS (HR 0.62; 95% CI 0.28-1.35). Among 44 patients with pathologic stage II disease, 7 had a recurrence (4 SH and 3 RH); 6 of 7 had distant recurrences.

Conclusions: Fifty-one percent of patients with clinical stage II endometrial cancer had advanced disease on final pathology, highlighting the importance of surgical staging. RH was not associated with RFS or reduced morbidity. Most recurrences were distant. Although RH could be performed to achieve negative surgical margins, SH may be sufficient for central, small tumours given the high risk of advanced disease and distant recurrence. Research efforts should further elucidate the ideal management of these patients.
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http://dx.doi.org/10.1016/j.jogc.2020.12.017DOI Listing
May 2021

Does prophylactic ureteric stenting at the time of colorectal surgery reduce the risk of ureteric injury? A systematic review and meta-analysis.

Colorectal Dis 2021 May 23;23(5):1060-1070. Epub 2021 Jan 23.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.

Aim: Cystoscopic placement of ureteric stents during colorectal surgery (CRS) may aid in the intraoperative identification of the ureters and thus prevent ureteric injury, but may also be associated with prolonged operating time, increased cost and adverse events. No formal recommendations exist regarding the use of ureteric stents prior to CRS. Our aim was to determine the effect of prophylactic ureteric stent insertion on the risk of ureteric injury among adult patients undergoing CRS.

Method: A systematic search using the Ovid platform was completed. The primary outcome was risk of ureteric injury. Secondary outcomes included the risk of acute kidney injury (AKI), urinary tract infection (UTI), sepsis, length of stay (LOS) and mortality. The Paule-Mandel pooling and a random effects model was used to produce odds ratios (ORs) with 95% confidence intervals (CIs) for binary outcomes. Standardized mean differences (MD) were reported for continuous variables. Analyses were completed using R3.5.

Results: Nine retrospective cohort studies evaluating 98 507 patients were included. The incidence of ureteric injury was 0.6%. Overall, 5.1% of patients underwent ureteric stenting. There was no change in the odds of ureteric injury among stented patients compared with controls (OR 1.30, 95% CI 0.39-4.29, I  = 25%). Operating time was significantly longer (MD 49.3 min, 95% CI 35.3-63.4, I  = 96%) in the intervention group. There was no difference in rates of AKI, UTI, sepsis, LOS or mortality between groups.

Conclusion: Given the retrospective nature of the identified studies, the benefit of prophylactic ureteric stenting remains uncertain. Prophylactic ureteric stenting was not associated with increased patient morbidity but did significantly increase operating time.
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http://dx.doi.org/10.1111/codi.15498DOI Listing
May 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

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

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

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

Does small volume metastatic lymph node disease affect long-term prognosis in early cervical cancer?

Int J Gynecol Cancer 2020 03 22;30(3):285-290. Epub 2019 Dec 22.

Gynecologic Oncology, Toronto Sunnybrook Regional Cancer Center, Toronto, Ontario, Canada

Introduction: As sentinel lymph node biopsy is evolving to an accepted standard of care, clinicians are being faced with more frequent cases of small volume nodal metastatic disease. The objective of this study is to describe the management and to measure the effect on recurrence rates of nodal micrometastasis and isolated tumor cells in patients with early stage cervical cancer at two high-volume centers.

Methods: We conducted a review of prospectively collected patients with surgically treated cervical cancer who were found to have micrometastasis or isolated tumor cells on ultrastaging of the sentinel lymph node. Our practice is to follow patients for ≥5 years post-operatively either at our center or another cancer center closer to home.

Results: Nineteen patients with small volume nodal disease were identified between 2006 and 2018. Median follow-up was 62 months. Ten (53%) had nodal micrometastatic disease, while nine (47%) had isolated tumor cells detected in the sentinel lymph node. Seven patients (37%) underwent completion pelvic lymphadenectomy and four of them also had para-aortic lymphadenectomy; there were no positive non-sentinel lymph nodes. The majority (74%) received adjuvant treatment, mostly driven by tumor factors. We observed two recurrences. Recurrence-free survival was comparable with historical cohorts of node negative patients, and adjuvant treatment did not seem to impact the recurrence rate (p=0.5).

Conclusion: Given the uncertainties around the prognostic significance of small volume nodal disease in cervical cancer, a large proportion of patients receive adjuvant treatment. We found no positive non-sentinel lymph nodes, suggesting that pelvic lymphadenectomy or para-aortic lymphadenectomy may not be of benefit in patients diagnosed with small volume nodal metastases. Recurrence-free survival in this group did not seem to be affected. However, given the small numbers of patients and lack of level 1 evidence, decisions should be individualized in accordance with patient preferences and tumor factors.
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http://dx.doi.org/10.1136/ijgc-2019-000928DOI Listing
March 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

Histological grading of ovarian mucinous carcinoma - an outcome-based analysis of traditional and novel systems.

Histopathology 2020 Jul 29;77(1):26-34. Epub 2020 May 29.

Department of Laboratory Medicine, Sunnybrook Health Science Centre and University of Toronto, Toronto, ON, Canada.

Aims: Grading of primary ovarian mucinous carcinoma (OMC) is inconsistent among practices. The International Collaboration on Cancer Reporting recommends grading OMC using the International Federation of Gynecology and Obstetrics (FIGO) system for endometrial endometrioid carcinoma, when needed. The growth pattern (expansile versus infiltrative), a known prognostic variable in OMC, is not considered in any grading system. We herein analysed the prognostic value of various grading methods in a well-annotated cohort of OMC.

Methods And Results: Institutional OMCs underwent review and grading by the Silverberg and FIGO schemes and a novel system, growth-based grading (GBG), defined as G1 (expansile growth or infiltrative invasion in ≤10%) and G2 (infiltrative growth >10% of tumour). Of 46 OMCs included, 80% were FIGO stage I, 11% stage II and 9% stage III. On follow-up (mean = 52 months, range = 1-190), five patients (11%) had adverse events (three recurrences and four deaths). On univariate analysis, stage (P = 0.01, Cox proportional analysis), Silverberg grade (P = 0.01), GBG grade (P = 0.001) and percentage of infiltrative growth (P < 0.001), but not FIGO grade, correlated with disease-free survival. Log-rank analysis showed increased survival in patients with Silverberg grade 1 versus 2 (P < 0.001) and those with GBG G1 versus G2 (P < 0.001). None of the parameters evaluated was significant on multivariate analysis (restricted due to the low number of adverse events).

Conclusions: Silverberg and the new GBG system appear to be prognostically significant in OMC. Pattern-based grading allows for a binary stratification into low- and high-grade categories, which may be more appropriate for patient risk stratification. Despite current practices and recommendations to utilise FIGO grading in OMC, our study shows no prognostic significance of this system and we advise against its use.
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http://dx.doi.org/10.1111/his.14039DOI Listing
July 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

Impact of surgical approach on oncologic outcomes in women undergoing radical hysterectomy for cervical cancer.

Am J Obstet Gynecol 2019 12 6;221(6):619.e1-619.e24. Epub 2019 Jul 6.

Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON, Canada; Division of Gynecologic Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address:

Background: Recent studies demonstrating shorter survival among cervical cancer patients undergoing minimally invasive versus open radical hysterectomy could not account for surgeon volume and require confirmation in other jurisdictions with larger sample sizes, longer follow-up, and data on disease recurrence.

Objective: To determine if surgical approach is associated with oncologic outcomes in cervical cancer patients undergoing minimally invasive or open radical hysterectomy, while accounting for mechanistic factors including surgeon volume.

Study Design: We performed a population-based retrospective cohort study of cervical cancer patients undergoing primary radical hysterectomy by a gynecologic oncologist from 2006 to 2017 in Ontario, Canada. A multivariable marginal Cox proportional hazards model and cause-specific hazards model were used to evaluate the association of surgical approach with all-cause death and recurrence respectively, clustering at the surgeon level. We tested for interactions between surgical approach and either pathologic stage or surgeon volume.

Results: We identified 958 patients (minimally invasive 475; open 483) with mean age 45.9 and a median follow-up of 6 years. Of minimally invasive procedures, 89.6% were performed laparoscopically and 10.4% robotically. The unadjusted 5-year cumulative incidences of all-cause death (minimally invasive 12.5%; open 5.4%), cervical cancer death (minimally invasive 9.3%; open 3.3%), and recurrence (minimally invasive 16.2%; open 8.4%) were significantly increased for minimally invasive radical hysterectomy in patients with stage IB disease, but not the cohort overall. After adjusting for patient factors and surgeon volume, minimally invasive radical hysterectomy was associated with increased rates of death (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.15-4.19) and recurrence (HR, 1.97; 95% CI, 1.10-3.50) compared to open radical hysterectomy in patients with stage IB disease (n = 534), but not IA disease (n = 244; HR, 0.73; 95% CI, 0.13-4.01; HR, 0.34; 95% CI, 0.10-1.10).

Conclusion: Minimally invasive radical hysterectomy is associated with increased rates of death and recurrence in patients with stage IB cervical cancer even after controlling for surgeon volume; open radical hysterectomy should be the recommended approach in this population. Although there may be a subset of patients with microscopic early-stage disease for whom minimally invasive radical hysterectomy remains safe, additional studies are required.
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http://dx.doi.org/10.1016/j.ajog.2019.07.009DOI 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

Uptake of sentinel lymph node procedures in women with vulvar cancer over time in a population based study.

Gynecol Oncol 2019 06 12;153(3):574-579. Epub 2019 Mar 12.

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

Objectives: To evaluate trends in uptake of sentinel lymph node (SLN) procedures over time and associated factors in women with vulvar cancer.

Methods: A retrospective population-based cohort study identified women with invasive squamous cell carcinoma (SCC) of the vulva using health administrative data for the province of Ontario, Canada, between 2008 and 2016. Patients who underwent SLN procedures were compared to those who had groin node dissection (GND). Multivariable analysis was used to identify factors associated with SLN procedures.

Results: 1385 patients with SCC of the vulva were identified; 1079 had a surgical procedure. Only those with groin node assessment were included in the study cohort (n = 732, 68%). SLN procedures were done in 52%. When comparing SLN versus GND, the rate of SLNs was significantly different by year of diagnosis (P < 0.001), associated comorbidity (P < 0.001) and institution (P < 0.0001). The rates of SLNs by institution with gynecologic oncologist were variable and ranged from 32% to 79% among 9 centers. There were no differences in age, income quintile, and urban/rural residence. The proportion of SLN procedures increased from 30.1% (CI 18.9-45.6) in 2008 to 65.2% (CI 36.5-107.6) in 2016. On multivariate analysis, factors significantly associated with SLN procedures were more recent year of diagnosis (OR 7.9, CI 2.7-23.5) associated comorbidities (OR 2.7, CI 1.5-5.0) and institution (Site 5, OR 19.6 [CI 3.6-108.3] and Site 6, [OR 6, CI 1.1-33.4]).

Conclusions: The proportion of SLN procedures in women with vulvar cancer has increased over time, but uptake is not uniform across institutions. Barriers to uptake should be explored.
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http://dx.doi.org/10.1016/j.ygyno.2019.03.010DOI Listing
June 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

Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial.

Lancet Oncol 2018 10 22;19(10):1394-1403. Epub 2018 Aug 22.

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Background: Accurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity. We sought to establish whether indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers.

Methods: In this non-inferiority, within-patient comparison study, patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualised by white light) followed by indocyanine green (visualised by near-infrared imaging), or indocyanine green followed by isosulfan blue dye. Permuted block randomisation with stratification by study site was done with a computerised random number generator. All participants were masked to their randomisation assignment until after the procedure; however, investigators were not masked to the procedure used. Laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI, USA) was used in all cases. The primary outcome was efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging versus that of isosulfan blue dye in the identification of lymph nodes, defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised. The study had a 5% non-inferiority margin needed to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level. Analyses were done in both per-protocol and modified intention-to-treat populations. The trial was registered with ClinicalTrials.gov, number NCT02209532, and is completed and closed.

Findings: Between Dec 21, 2015, and June 19, 2017, 180 patients were enrolled and randomly assigned to the two groups (90 to each group); 176 patients received the intervention and were evaluable (modified intention-to-treat population). 13 patients with major protocol violations were subsequently excluded from the per-protocol population. 517 sentinel nodes were identified in the per-protocol population (n=163), of which 478 (92%) were confirmed to be lymph nodes on pathological processing: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0·33). Seven sentinel lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. In total, 471 (97%) of 485 lymph nodes were identified with the green dye and 226 (47%) with the blue dye (difference 50%, 95% CI 39-62; p<0·0001). In the modified intention-to-treat population (n=176), 545 nodes were identified, of which 513 (94%) were confirmed to be lymph nodes on pathological processing: 229 (92%) of 248 nodes that were both blue and green, all nine nodes that were blue only, and 266 (95%) of 279 nodes that were green only (p=0·30). Nine sentinal lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. 495 (96%) of 513 nodes were identified with the green dye and 238 (46%) with the blue dye (50%, 39-61; p<0·0001).

Interpretation: Indocyanine green dye with near-infrared fluorescence imaging identified more sentinel nodes than isosulfan blue dye in women with cervical and uterine cancers, with no difference in the pathological confirmation of nodal tissue between the two mapping substances.

Funding: Novadaq.
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http://dx.doi.org/10.1016/S1470-2045(18)30448-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580418PMC
October 2018

Prospective cohort study comparing quality of life and sexual health outcomes between women undergoing robotic, laparoscopic and open surgery for endometrial cancer.

Gynecol Oncol 2018 06 19;149(3):476-483. Epub 2018 Apr 19.

Division of Gynecologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, Canada.

Objective: To evaluate patient-reported outcomes (PROs) between women treated by laparoscopic, robotic and open approaches for endometrial cancer.

Methods: Prospective cohort study comparing PRO at baseline, short- (1 and 3 weeks) and long-term (12 and 24 weeks) follow-up postoperatively. Quality of life (QOL) measures were the Functional Assessment of Cancer Therapy (FACT-G), EuroQol Five Dimensions (EQ-5D), and Brief Pain Inventory (BPI). Sexual health measures were the Female Sexual Function Index (FSFI) and the Sexual Adjustment and Body Image Scale for Gynecologic Cancer (SABIS-G).

Results: 468 eligible patients (laparotomy = 92, laparoscopy = 152, robotic = 224) were recruited. There were no significant differences between the laparoscopy and robotic groups for any PRO (P > 0.05). At short-term follow-up, patients who underwent minimally invasive surgery (robotic or laparoscopy) had significantly higher FACT-G (P < 0.0001) and EQ-5D (P < 0.0001) scores, with less pain (P = 0.02) and improved pain interference (P = 0.0008), than patients undergoing laparotomy. At long-term follow-up, there were sustained improvements in the FACT-G (P = 0.035) and the health state EQ-5D visual analogue scale (P = 0.022). Surgical approach had no impact on sexual health (P > 0.05); however the mean FSFI score for the entire cohort met clinical cut-offs for sexual dysfunction.

Conclusion: Minimally invasive approaches result in improved QOL beyond the short-term postoperative period, with benefits noted up to 12 weeks after surgery. This prolonged QOL advantage provides further evidence that MIS should be the standard surgical approach for women with early stage endometrial cancer.
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http://dx.doi.org/10.1016/j.ygyno.2018.04.558DOI Listing
June 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

A Multicentre Retrospective Review of Clinical Characteristics of Uterine Sarcoma.

J Obstet Gynaecol Can 2017 Aug;39(8):652-658

Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, ON. Electronic address:

Objective: Professional societies have recently urged gynaecologists to counsel patients about the risks of encountering uterine sarcoma at fibroid surgery especially when morcellation is used. Our objective was to learn the preoperative and postoperative characteristics of patients with uterine sarcoma to better counsel patients undergoing surgery for presumably benign fibroids.

Methods: This is a multicentre, retrospective cohort study. Three academic tertiary cancer centres in Southern Ontario over a 13-year period (2001-2014). Patients diagnosed with leiomyosarcoma or endometrial stromal sarcoma were included after identification using pathology databases. A retrospective chart review was conducted to determine clinical characteristics and survival data.

Results: The study included 302 patients with uterine sarcomas (221 leiomyosarcomas, 81 endometrial stromal sarcomas). Mean age at diagnosis was 55 years, and 59% were postmenopausal. Sarcoma diagnosis was made following endometrial sampling (25%), hysterectomy (69% laparotomy, 2.7% laparoscopic/vaginal), and myomectomy (3.3%). Of all the patients who underwent endometrial sampling, 65% were diagnosed with a uterine sarcoma in this manner. A general gynaecologist performed the primary surgical procedure in 166 of 302 patients (55%). Tumour disruption at the time of primary surgery occurred in 57 of 295 patients (19%): subtotal hysterectomy (21), myomectomy (10), dissection of adherent tumour (17), and morcellation (9). Morcellation, to facilitate a minimally invasive approach, was performed with scalpel (2 at laparotomy, 5 vaginally) and with a laparoscopic electro-mechanical morcellator (2). At a median follow-up of 2.9 years, there was no significant difference in survival for stage I and II patients with tumour disruption (n = 32) compared with those without tumour disruption (n = 143), regardless of sarcoma type (P = 0.6).

Conclusion: The majority of patients with uterine sarcomas were postmenopausal. Many can be diagnosed preoperatively with endometrial sampling. Forty-one percent of patients with uterine sarcomas had a high preoperative index of suspicion, resulting in intervention by an oncologist. Morcellation with laparoscopic electro-mechanical morcellator was rare.
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http://dx.doi.org/10.1016/j.jogc.2017.03.090DOI Listing
August 2017

Endometrioid Carcinoma of the Ovary: Outcomes Compared to Serous Carcinoma After 10 Years of Follow-Up.

J Obstet Gynaecol Can 2017 Jan 10;39(1):34-41. Epub 2016 Dec 10.

Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of Toronto, Toronto ON; Division of Gynaecologic Oncology, Odette Cancer Centre, University of Toronto, Toronto ON.

Objectives: The prognostic significance of endometrioid ovarian cancer is unclear. In this study we compared rates of overall survival (OS) and disease-free survival between patients with endometrioid and serous ovarian cancers using long-term follow-up data.

Methods: We included patients with endometrioid or serous ovarian cancers diagnosed at a single regional cancer centre between 1988 and 2006. Data on baseline and treatment characteristics were collected retrospectively. We used multivariate Cox proportional hazard models to determine the independent effect of histology on death or recurrence, adjusting for age, tumour grade, primary cytoreductive surgery, year of diagnosis, adjuvant treatment, and stage.

Results: Five hundred and thirty-three women with ovarian cancer were included in the study cohort; 98 (18.4%) had endometrioid histology and 435 (81.6%) serous histology. The five-year OS rate for women with endometrioid cancer was 80.6%, and for women with serous ovarian cancer, it was 35.0%. The 10-year OS rates were 68.4% and 18.4% for endometrioid and serous histology, respectively. After adjusting for confounders excluding stage, there was a significantly lower risk of death from endometrioid cancer compared to serous ovarian cancer (hazard ratio [HR] 0.41, 95% CI 0.26 to 0.66). However, the difference was no longer significant after adding tumour stage to the model (HR 0.74, 95% CI 0.45 to 1.24). We found similar results for the risk of recurrence (HR 0.41, 95% CI 0.27 to 0.62 with stage not included, compared to HR 0.77, 95% CI 0.49 to 1.21 with stage included).

Conclusion: In this large cohort, in comparison with women with serous ovarian cancer, women with endometrioid ovarian cancer presented at a younger age, had earlier stage disease, and had disease almost always confined to the pelvis. The earlier stage of presentation of endometrioid ovarian cancer resulted in improved five-year and 10-year OS rates compared to serous ovarian cancer.
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http://dx.doi.org/10.1016/j.jogc.2016.10.006DOI Listing
January 2017

Does a groin node dissection in vulvar cancer affect groin recurrence and overall survival?: Results from a population-based cohort study.

Gynecol Oncol 2017 Feb 16;144(2):318-323. Epub 2016 Nov 16.

University of Toronto, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Department of Radiation Oncology, Odette Cancer Centre, Toronto, Ontario, Canada.

Background: To determine, in a population-based cohort of vulvar cancer patients, if groin node dissection (GND) decreases the risk of groin recurrence and increases overall survival.

Methods: This population-based retrospective cohort study includes all cases of invasive squamous cell carcinoma identified in a provincial cancer registry from 1998 to 2007. Data collection was completed for all clinical and pathologic factors by chart abstraction. Cumulative incidence functions for recurrence were estimated, accounting for death before recurrence as a competing risk. Multivariable Cox regression models examined the associations between GND and groin recurrence, and overall survival.

Results: Clinical and pathologic data were collected for 1109 patients, of which 1038 patients were eligible for GND. 647 patients (62%) had a GND, while 391 patients (38%) did not. Median follow-up was 2.8years. Cumulative incidence plots demonstrate that the risk of death without recurrence was consistently higher than groin recurrence in each year after diagnosis. On multivariate analysis, GND was not significantly associated with decreased groin recurrence (HR 0.91, 95% CI 0.58-1.44, p=0.70). The hazard of death was 15% lower for women who received GND (HR 0.85, 95% CI 0.63-1.16, p=0.32), but this difference was not statistically significant.

Conclusions: There was no significant difference in groin recurrence or overall survival in those with or without GND in this population-based cohort, raising questions whether a subgroup of patients may not benefit from GND. Patients had a higher probability of dying before groin recurrence could occur. Future trial design should consider death as a competing risk.
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http://dx.doi.org/10.1016/j.ygyno.2016.11.026DOI Listing
February 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
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