Publications by authors named "Soyoun Rachel Kim"

17 Publications

  • Page 1 of 1

The correlation between BRCA status and surgical cytoreduction in high-grade serous ovarian carcinoma.

Gynecol Oncol 2021 Sep 10;162(3):702-706. Epub 2021 Jul 10.

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. Electronic address:

Objective: BRCA-associated ovarian cancers are biologically unique; it is unclear if this translates to favorable outcomes at the time of primary cytoreduction (PCS). The aim of this study was to compare the amount of residual disease after PCS in BRCA mutated (BRCAm) and wild-type (BRCAwt) high-grade serous ovarian cancers (HGSC), and to assess whether BRCA status was an independent predictor of complete cytoreduction.

Methods: We conducted a retrospective analysis of patients with stage III/IV HGSC with known germline and somatic BRCA status, treated with PCS from 2000 to 2017. We compared the complete, optimal and suboptimal cytoreduction rates between the BRCAm and BRCAwt cohorts and built a predictive model to assess whether BRCA status was predictive of complete cytoreduction.

Results: Of 303 treated with PCS, 120 were germline/somatic BRCAm (40%) and 183 were BRCAwt (60%). BRCAm women tended to be younger, but there were no differences between the two groups in preoperative CA-125, disease burden, surgical complexity, length of surgery, or perioperative complications. BRCAm group had a higher rate of complete cytoreduction to no residual disease (0 mm) [72% vs. 48%] (p < 0.001). In a multivariate model, after accounting for age, length of surgery, CA-125 level, stage, disease burden and surgical complexity, BRCAm status was predictive of 0 mm residual disease with odds ratio of 5.3 (95% CI 2.45-11.5; p < 0.001).

Conclusions: BRCAm status is predictive of complete cytoreduction at the time of PCS. Despite similar disease burden and surgical efforts, one is more likely to achieve complete resection in BRCAm HGSC.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.010DOI Listing
September 2021

Efficacy and toxicity of intraperitoneal chemotherapy as compared to intravenous chemotherapy in the treatment of patients with advanced ovarian cancer.

Int J Gynaecol Obstet 2021 Jul 2. Epub 2021 Jul 2.

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

Objective: To assess the efficacy and toxicity of intraperitoneal (IP) chemotherapy compared to intravenous (IV) chemotherapy.

Methods: Toxicity profiles, recurrence patterns, and long-term survival outcomes of 271 women with Stage IIIC or IV high-grade serous ovarian cancer (HGSC) treated with primary cytoreductive surgery followed by adjuvant IP or IV chemotherapy during 2001-2015 were reviewed.

Results: Women who received IP chemotherapy (n = 91) were more likely to have undergone aggressive and longer surgery with no residual disease compared to the IV arm (n = 180). Chemotherapy-related toxicities were comparable between the two groups. Extraperitoneal recurrences were more common in the IP arm compared to the IV arm. Five-year progression-free survival was 19% versus 18% (P = 0.63) and overall survival was 73% versus 44% (P < 0.01) in the IP versus IV arms, respectively. After adjustment for significant clinicopathologic factors in a multivariable model, use of IP was no longer a statistically significant predictor of overall survival.

Conclusion: IP chemotherapy in advanced HGSC has not been widely adopted due to concerns about toxicity and inconvenience. Use of IP chemotherapy was associated with comparable safety profile and efficacy to IV chemotherapy in women with Stage IIIC/IV HGSC. Recurrences were more likely to be extraperitoneal with IP treatment.
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http://dx.doi.org/10.1002/ijgo.13813DOI Listing
July 2021

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 of Canada (GOC) community of practice (CoP).

Gynecol Oncol 2021 Sep 26;162(3):606-612. Epub 2021 Jun 26.

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
September 2021

Management of Wolffian adnexal tumors.

Int J Gynecol Cancer 2021 06;31(6):925-928

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

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http://dx.doi.org/10.1136/ijgc-2020-002367DOI Listing
June 2021

Sentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics.

Am J Obstet Gynecol 2021 May 29. Epub 2021 May 29.

Division of Gynaecologic Oncology, Department of Obstetrics and Gynecology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objective: A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280).

Data Sources: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials.

Study Eligibility Criteria: We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data.

Methods: We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.

Results: We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44-82.5 years) and the study-level median body mass index was 28.6 kg/m (range, 19.4-43.7 kg/m). The pooled detection rates were 91% per patient (95% confidence interval, 85%-95%; I=59%) and 64% bilaterally (95% confidence interval, 53%-73%; I=69%). The overall node positivity rate was 26% (95% confidence interval, 19%-34%; I=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%-96%; I=0%), a false negative rate of 8% (95% confidence interval, 4%-16%; I=0%), and a negative predictive value of 97% (95% confidence interval, 95%-99%; I=0%).

Conclusion: Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.
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http://dx.doi.org/10.1016/j.ajog.2021.05.034DOI Listing
May 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 Sep 13;127(17):3082-3091. 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
September 2021

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

Gynecol Oncol 2021 04 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

The impacts of neoadjuvant chemotherapy and of cytoreductive surgery on 10-year survival from advanced ovarian cancer.

Int J Gynaecol Obstet 2021 Jun 13;153(3):417-423. Epub 2021 Jan 13.

Division of Gynecologic Oncology, Princess Margaret Cancer Center, University Health Networks, Toronto, ON, Canada.

Objective: To compare the long-term survival outcomes for women with advanced ovarian cancer treated with chemotherapy either before or after surgery (neoadjuvant chemotherapy vs primary cytoreductive surgery) at a single tertiary cancer center.

Methods: Retrospective cohort study of 326 patients with Stage IIIC or IV high-grade serous ovarian cancer who received neoadjuvant chemotherapy or primary cytoreductive surgery between 2001 and 2011. Clinical treatments were recorded and 10-year survival rates were measured.

Results: A total of 183 women (56.1%) underwent primary cytoreductive surgery and 143 women (43.9%) received neoadjuvant chemotherapy. Women who received neoadjuvant chemotherapy were more likely to have no residual disease than those who underwent primary cytoreductive surgery (51.4% vs 41.5%; P = 0.030) but experienced inferior 10-year overall survival (9.1% vs 19.3%; P < 0.001). Among those who had primary cytoreductive surgery, those with no residual disease had superior 10-year overall survival than those who had any evidence of residual disease (36.0% vs 7.2%; P < 0.001).

Conclusion: Among women with advanced ovarian cancer, those who underwent primary cytoreductive surgery had better survival than those who received neoadjuvant chemotherapy. Neoadjuvant chemotherapy should be reserved for those in whom optimal primary cytoreductive surgery is not feasible.
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http://dx.doi.org/10.1002/ijgo.13542DOI Listing
June 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

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

Mismatch repair deficiency and prognostic significance in patients with low-risk endometrioid endometrial cancers.

Int J Gynecol Cancer 2020 06 30;30(6):783-788. Epub 2020 Apr 30.

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

Objectives: Mismatch repair deficiency is observed in 25%-30% of all endometrial cancers. This can be detected by the absence of mismatch repair protein staining on immunohistochemistry, and is used as a screen for Lynch syndrome. Only 10% of women with mismatch repair deficiency have Lynch syndrome, but mismatch repair deficiency may still have prognostic significance. The objective of this study was to compare clinical outcomes between mismatch repair-deficient and mismatch repair-proficient low-risk endometrioid endometrial cancers (stage IA, grade 1 or 2).

Methods: This was a retrospective population-based cohort study of all low-risk endometrioid endometrial cancers (stage IA, grade 1 or 2) from the Vancouver Coastal Health Authority region from February 2011 to January 2016 that were assessed for mismatch repair deficiency. Any other histology, stage, or grade was excluded from the study. Primary outcome measures were progression-free survival and overall survival calculated using Kaplan-Meier method and log-rank tests. Cox proportional hazards model estimated the association between mismatch repair deficiency and recurrence and death after adjustment for covariates, expressed as hazard ratios (HRs). Secondary outcome measures were recurrence rates expressed per 100 person-years (p100py).

Results: There were 475 patients diagnosed with low-risk endometrioid endometrial cancer, including 131 with mismatch repair-deficient (27.6%) and 344 with mismatch repair-proficient (72.4%) tumors. Women with mismatch repair-deficient tumors had worse progression-free survival (24 months; p=0.0082) and higher recurrence rates (3.56 p100py) compared with those with mismatch repair-proficient tumors (27 months; 1.21 p100py, p=0.04). The absolute number of recurrences was overall low. There were 11 recurrences out of 131 mismatch repair-deficient cases (8.4%) and 14 out of 344 mismatch repair proficient cases (4.1%). After adjustment for age, lymphovascular space invasion status, adjuvant therapy, and post-operative grade, mismatch repair-deficient status remained associated with a higher risk of recurrence (HR 3.56, 95% CI 2.01 to 5.95). There was no significant difference in overall survival between mismatch repair groups (mismatch repair-proficient group 27.5 months vs 25.0 months in the deficient group) (HR 1.23, 95% CI 0.49 to 3.10).

Conclusion: In low-risk stage IA grade 1 or 2 endometrioid endometrial cancers, mismatch repair deficiency is associated with a higher recurrence rate than mismatch repair proficiency after adjustment for covariates, implying that mismatch repair deficiency reflects a different biology in endometrial cancer.
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http://dx.doi.org/10.1136/ijgc-2019-000910DOI Listing
June 2020

Molecular subtypes of clear cell carcinoma of the endometrium: Opportunities for prognostic and predictive stratification.

Gynecol Oncol 2020 07 21;158(1):3-11. Epub 2020 Apr 21.

Department of Obstetrics and Gynecology, Division of Gynecology Oncology, University of British Columbia, Vancouver, BC, Canada; BC Cancer Agency, Vancouver, BC, Canada. Electronic address:

Objective: Our aim was to characterize the pathological, molecular and clinical outcomes of clear cell carcinoma of the endometrium (CCC).

Methods: CCC underwent ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification identifying four molecular subtypes: i) 'POLEmut' for ECs with pathogenic POLE mutations, ii) 'MMRd', if there is loss of mismatch repair proteins by immunohistochemistry (IHC), iii) 'p53wt' or iv) 'p53abn' based on p53 IHC staining. Clinicopathologic parameters, immune markers (CD3, CD8, CD79a, CD138, PD-1), ER, L1CAM, and outcomes were assessed.

Results: 52 CCCs were classified, including 1 (2%) POLEmut, 5 (10%) MMRd, 28 (54%) p53wt and 18 (35%) p53abn. Women with p53abn and p53wt CCCs were older than women with MMRd and POLEmut subtypes. p53wt CCC were distinct from typical p53wt endometrioid carcinomas; more likely to arise in older, thinner women, with advanced stage disease, LVSI and lymph node involvement, and a higher proportion ER negative, L1CAM overexpressing tumors with markedly worse outcomes. High levels of immune infiltrates (TIL) were observed in 75% of the CCC cohort. L1CAM overexpression was highest within p53abn and p53wt subtypes of CCC.

Conclusion: CCC is a heterogeneous disease encompassing all four molecular subtypes and a wide range of clinical outcomes. Outcomes of patients with POLEmut, MMRd and p53abn CCC are not distinguishable from those of other patients with these respective subtypes of EC; p53wt CCC, however, differ from endometrioid p53wt EC in clinical, pathological, molecular features and outcomes. Thus, p53wt CCC of endometrium appear to be a distinct clinicopathological entity within the larger group of p53wt ECs.
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http://dx.doi.org/10.1016/j.ygyno.2020.04.043DOI Listing
July 2020

Utility of 18F-FDG-PET/CT imaging in patients with recurrent gynecological malignancies prior to pelvic exenteration.

Int J Gynecol Cancer 2019 Mar 28. Epub 2019 Mar 28.

Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada

Background: In patients with recurrent gynecologic malignancies isolated to the pelvis, pelvic exenteration is a potential option. 18F-Fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT), is often used to confirm no evidence of metastatic disease.

Objective: To assess the impact of PET/CT on clinical management of patients with recurrent gynecologic malignancies being considered for pelvic exenteration.

Methods: Patients with recurrent gynecological malignancies who underwent PET/CT imaging between 2011 and 2014 were identified. All were considered for pelvic exenteration and underwent conventional imaging with CT +/- pelvic MRI. Patient anthropometric data, disease sites, histology, stage, treatment received, and treatment plan based on PET/CT findings were extracted.

Results: A total of 40 patients met inclusion criteria. In 15 (37.5%) of these patients, results of PET/CT changed the original plan of pelvic exenteration owing to metastatic disease/unresectability (11/15) or no evidence of disease on PET/CT imaging (4/15). Twenty-five (62.5%) patients had their planned surgery after PET/CT with 19 (76%) patients undergoing a completed exenteration procedure. Six (24%) patients with PET/CT indicating isolated pelvic recurrence ultimately had intra-operative findings of extra-pelvic metastasis or nodal disease and therefore the planned surgery was aborted.

Conclusion: In nearly 40% of patients with recurrent gynecologic malignancies being considered for radical salvage surgery, PET/CT can significantly alter the originally intended treatment and hence may reduce the number of futile surgical procedures.
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http://dx.doi.org/10.1136/ijgc-2018-000091DOI Listing
March 2019

Does MMR status in endometrial cancer influence response to adjuvant therapy?

Gynecol Oncol 2018 10 29;151(1):76-81. Epub 2018 Aug 29.

BC Cancer Agency, Vancouver, BC, Canada; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Vancouver, BC, Canada. Electronic address:

Objective: Mismatch repair (MMR) deficiency occurs in 20-40% of endometrial cancers but its therapeutic implication remains uncertain. Our objective was to compare clinical outcomes after adjuvant therapy between MMR deficient and proficient endometrial cancers from a population-based study.

Methods: This was a retrospective population-based cohort study of all endometrial cancers from the Vancouver Coastal Health authority region from 2011 to 2016, for which adjuvant therapy (radiotherapy and/or chemotherapy) was administered. Primary outcome measure was recurrence rates, expressed per 100 person-years (p100 py). Progression free survival (PFS) and overall survival (OS) rates were compared using Kaplan-Meier method and log-rank tests, and covariates were evaluated using Cox proportional hazards regression.

Results: There were 535 patients who received adjuvant therapy (radiotherapy and/or chemotherapy), including 162 (30.3%) and 373 (69.7%) with MMR-deficient and proficient tumors, respectively. Demographic variables were similar except MMR-deficient patients were younger (62.0 vs. 64.8, p = 0.01). Patients with MMR-deficient tumors were more likely to have endometrioid histotype (85.8% vs. 61.4%), more likely to have Stage I disease (62.3% vs 54.7%), and LVSI (65.4% vs. 53.4%) compared to those with MMR-proficient tumors. There was a trend for MMR-proficient group to have higher recurrence rates (10.7 p100 py vs 5.9 p100 py) and MMR deficiency was associated with better OS and PFS, but on multivariable analysis, MMR status was no longer significant.

Conclusion: Women with MMR-deficient endometrial cancers who receive adjuvant therapy have a lower rate of recurrence compared to those with MMR-proficient cancers. However, on multivariable analysis, MMR status does not remain associated with differences in PFS or OS.
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http://dx.doi.org/10.1016/j.ygyno.2018.08.020DOI Listing
October 2018

Fertility-Sparing Management Using Progestin for Young Women with Endometrial Cancer From a Population-Based Study.

J Obstet Gynaecol Can 2018 Mar 3;40(3):328-333. Epub 2017 Oct 3.

BC Cancer Agency, Vancouver, BC; Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC.

Objective: For young women with complex atypical endometrial hyperplasia (CAH) and endometrial cancer (EC) who choose to preserve fertility, progestin therapy is the mainstay of treatment. The objective of this study was to evaluate oncologic and reproductive outcomes associated with progestin therapy among these women from a population-based cancer registry.

Methods: This was a retrospective population-based cohort study of women under age 45 in British Columbia from 2003 to 2015 with CAH or grade I endometrioid EC who used progestins as initial management. Demographics, treatment type, response to treatment, determinants of definitive surgery (hysterectomy), pathologic findings, and obstetrical outcomes were reviewed.

Results: There were 50 women under age 45 with CAH (n = 29) and EC (n = 21). Median age at diagnosis was 36 years (range 25-41), and most were nulliparous (88%) with a median BMI of 32.9 (range 21-70). After 6 months of therapy, 58% of women had persistent disease, and only 35% had full resolution at last follow-up (median 23 months). There were 32 women who had a hysterectomy, including 27 because of persistent/recurrent disease, and 5 who chose surgery despite complete response to progestins. The majority of hysterectomy specimens (85%) had minimal or no residual pathology, even among those with disease on preoperative biopsy. Only 10% of women had successful pregnancies.

Conclusion: There is a moderate to high risk of persistence of CAH or EC on progestin therapy. However, for those undergoing hysterectomy, the vast majority has low-risk disease confined to the endometrium, implying the possibility of further conservative management of persistent disease.
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http://dx.doi.org/10.1016/j.jogc.2017.06.037DOI Listing
March 2018

Uptake of a women-only, sex-work-specific drop-in center and links with sexual and reproductive health care for sex workers.

Int J Gynaecol Obstet 2015 Mar 27;128(3):201-5. Epub 2014 Nov 27.

Gender and Sexual Health Initiative, BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada. Electronic address:

Objective: To longitudinally examine female sex workers' (FSWs') uptake of a women-only, sex-work-specific drop-in service and its impact on their access to sexual and reproductive health (SRH) services.

Methods: For the present longitudinal analysis, data were drawn from the AESHA (An Evaluation of Sex Workers' Health Access) study, a community-based, open, prospective cohort of FSWs from Vancouver, BC, Canada. Data obtained between January 2010 and February 2013 were analyzed. Participants are followed up on a semi-annual basis. Multivariable logistic regression using generalized estimating equations was used to identify correlates of service uptake.

Results: Of 547 FSWs included in the present analysis, 330 (60.3%) utilized the services during the 3-year study period. Service use was independently associated with age (adjusted odds ratio [AOR] 1.04; 95% confidence interval [CI] 1.03-1.06), Aboriginal ancestry (AOR 2.18; 95% CI 1.61-2.95), injection drug use (AOR 1.67; 95% CI 1.29-2.17), exchange of sex for drugs (AOR 1.40; 95%CI 1.15-1.71), and accessing SRH services (AOR 1.65; 95% CI 1.35-2.02).

Conclusion: A sex-work-specific drop-in space for marginalized FSWs had high uptake. Women-centered and low-threshold drop-in services can effectively link marginalized women with SRH services.
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http://dx.doi.org/10.1016/j.ijgo.2014.09.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329272PMC
March 2015
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