ORAL PRESENTATIONS | EXPOSÉS
O-ENDO-CLI-FEL-001 ��������������������������������������������������������������� RETHINKING PREOPERATIVE THERAPY FOR CLINICAL STAGE 2 ENDOMETRIAL CANCER M. Lee British Columbia Cancer Agency, Gynecologic Oncology, 600 W10th Ave, Vancouver, BC, V5Z 4E6, Canada J. Kwon, C. Aquino-Parsons, P. Hoskins, P. Lim Objectives: To review outcomes of women receiving preoperative radiotherapy for clinical stage 2 endometrial cancer in British Columbia. Study Methods: Retrospective population-based cohort study of clinical Stage 2 endometrial cancer patients referred to the British Columbia Cancer Agency (BCCA) from 2000 to 2008. Patient demographics, tumor factors, timing and details of treatments, and timing and sites of recurrence were obtained from BCCA patient records. Median disease-free survival and overall survival were calculated from the start of radiation to date of recurrence, death, or last follow-up. Results: Twenty-nine patients had preoperative pelvic radiotherapy followed by TAHBSO. Mean age at diagnosis was 62 years (range 41-83). Median follow-up was 3.1 years (0.3-5.3 years). The 3-year OS was 79%, and median DFS was 2.5 years (range 0.3-5.3 years). Eight patients recurred (27.6%) with a median time to recurrence of 1.3 years, (range 0.4-2.7 years. Six of these 8 patients who recurred had 2 high risk factors on uterine pathology (n=4), ovarian involvement, or high risk histological type. Only 1 of 21 patients who did not recur had a similar risk profile. Seven out of 8 patients (87.5%) had recurrences outside of the radiated field, but 2 of 8 patients also had recurrences within the radiated volume. Conclusions: Patients with clinical Stage 2 endometrial cancer who recurred were more likely to have high-risk factors on uterine pathology, and these recurrences were more likely to be distant, suggesting the need for chemotherapy. Patients who are not eligible for primary surgery should be considered for tri-modality therapy.
O-ENDO-HPOL-MD-001 ����������������������������������������������������������� THE SIGNIFICANCE OF SURGICAL STAGING IN INTERMEDIATE RISK ENDOMETRIAL CANCER J. Kwon University of British Columbia, Obstetrics and Gynecology, F326 - 4500 Oak Street, Vancouver, BC, V6H 3V5, Canada M. Mazgani, D. Miller, T. Ehlen, M. Heywood, J. McAlpine, S. Finlayson, M. Plante, G. Stuart, M. Carey Objectives: The objective was to evaluate rates of nodal disease in endometrial cancer within risk groups based on uterine factors, and to estimate the rate of potential undertreatment and impact on survival if nodal status was unknown. Study Methods: This was a retrospective population-based cohort study of endometrioid-type endometrial cancer in British Columbia from 2005-09. All women with a preoperative grade 2/3 cancer underwent hysterectomy, bilateral salpingo-oophorectomy (HBSO) and lymphadenectomy, and those with intermediate- or high-risk disease based on uterine factors after HBSO alone underwent secondary lymphadenectomy. We compared rates of nodepositivity and potential undertreatment in each group if nodal status had been unknown (chi-square test), and estimated the survival benefit from lymphadenectomy. Results: There were 222 women who underwent primary or secondary lymphadenectomy. Median age was 65 (range 38-86) and median number of lymph nodes was 10 (range 2-39). Of the 66 women with intermediate-risk disease (grade 1/2 tumour
with deep myometrial invasion), 6 had nodal disease (9.1%) and received adjuvant chemotherapy. They remain disease-free after 24 months (range 8-55). They would not have qualified for chemotherapy based on uterine factors alone, and would have been undertreated compared to other risk groups (chisquare p=0.071). A survival benefit of 1% was estimated from lymphadenectomy. Conclusions: Women with a grade 1 or 2 tumour and deep myometrial invasion have a 9% risk of nodal disease. Lymphadenectomy is significant for this subgroup as they would have been undertreated based on uterine risk factors alone, although the survival benefit is limited.
O-ENDO-HPOL-MD-004 ���������������������������������������������������������� IDENTIFYING LYNCH SYNDROME IN WOMEN WITH ENDOMETRIAL CANCER J. Kwon University of British Columbia, Obstetrics and Gynecology, F326 - 4500 Oak Street, Vancouver, BC, V6H 3V5, Canada J. Scott, B. Gilks, M. Daniels, C. Sun, L. Karen Objectives: Women with Lynch syndrome have up to a 60% lifetime risk of endometrial cancer. Amsterdam II criteria are currently used to select individuals for genetic testing, but not all women with Lynch syndrome fulfill these criteria. We estimated the costs and benefits of different testing criteria to identify Lynch syndrome in women with endometrial cancer. Study Methods: We developed a Markov Monte Carlo simulation model to compare 3 strategies for Lynch syndrome testing in women with endometrial cancer: (1) Amsterdam II criteria; (2) age under 50 with at least 1 first-degree relative with a Lynchassociated cancer, and (3) immunohistochemistry (IHC) “triage” of endometrial cancers based on age and/or family history, followed by genetic testing if abnormal IHC results. Net health benefit was life expectancy, and primary outcome was the incremental costeffectiveness ratio (ICER). The model estimated the number of future colorectal cancers associated with each strategy. Results: Immunohistochemistry triage of endometrial cancers in women having 1 first-degree relative with a Lynch-associated cancer yielded a favourable ICER of $9,126 per year of life gained. This strategy would be more effective in identifying women with Lynch syndrome and potentially prevent more colorectal cancers in the future, while being less costly than Amsterdam II criteria. IHC triage of all endometrial cancers would be most effective but at considerable cost ($648,494 per year of life gained). Conclusions: Immunohistochemistry triage of endometrial cancers in women having at least 1 first-degree relative with a Lynchassociated cancer is a cost-effective strategy for detecting Lynch syndrome.
O-OTH-CLI-MD-001 �������������������������������������������������������������������� PREOPERATIVE BOWEL PREPARATION IN GYNECOLOGIC ONCOLOGY: A REVIEW OF PRACTICE PATTERNS AND AN IMPETUS TO CHANGE T. Wells University of Alberta, Department of Obstetrics and Gynecology, 201 Community Services Centre, 10240 Kingsway Avenue, Edmonton, AB, T5H 3V9, Canada M. Plante, J. McAlpine, the Communities of Practice Groups on behalf of the Society of Gynecologic Oncology of Canada Objectives: Mechanical bowel preparation (MBP) is commonly used in gynecologic oncology (GO). We wished to assess the practice patterns and beliefs within the GOC, review the literature on MBP
JUNE JOGC JUIN 2011 l S73
ORAL PRESENTATIONS | EXPOSÉS
as applicable to GO surgeries, and construct recommendations specific to our subspecialty. Study Methods: A 23 question, 10 minute internet survey was sent to 110 GOC members regarding the use, rationale, and understanding of the literature pertaining to MBP for GO surgeries. The historical justifications for using MBP prior to pelvic and abdominal surgery were identified through literature review. Results: Half of respondents (48%) routinely order MBP despite acknowledgement in 77% that there was no good evidence to support its use. Use encompassed all cancer sites (53% ovary, 32% endometrial, 27% cervical, 8% vulvar) and surgical approaches (43% laparotomy, 29% laparoscopy/robotics). The most common reasons for ordering MBP were to lower risk of anastomotic leak and improve visualization. In the last five years use of MBP has decreased in the majority (77%) of GOC members. 71% of respondents felt formal recommendations specific to the field of GO would be helpful. None of the arguments for using MBP could be justified in the literature. In contrast, common and often serious sequelae from MBP are frequently described. Admitted use of bowel preparation in other surgical specialties was even higher (53-99%) than within the GOC. Conclusions: There is no literature to support the routine use of MBP in GO. Published recommendations (herein) should support and guide change in practice.
O-OTH-INN-OTH-001 ���������������������������������������������������������������� GYNAECOLOGIC CANCER RISK MANAGEMENT IN WOMEN WITH LYNCH SYNDROME: PATIENT PERSPECTIVES FROM BRITISH COLUMBIA K. Turner BC Cancer Agency, Hereditary Cancer Program, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6, Canada J. Kwon, C. Portigal-Todd Objectives: To examine the attitudes and management practices of gynaecologic cancer risk in women with Lynch syndrome (LS) in British Columbia. Study Methods: There were 83 living females identified in the BC Cancer Agency database with a molecular diagnosis of LS in British Columbia (and the Yukon) from January 2004 – September 2009. Participants completed questionnaires that examined knowledge and availability of gynaecologic cancer risk and management options. Results: Forty-two participants returned completed questionnaires. The majority of participants (16/31) reported they received the most information regarding gynaecologic cancer risk and management options from a geneticist/genetic counsellor, and the median knowledge score of gynaecologic cancer risk and management options was 7 (range 3-10) on a 10-point scale. Of the women with uterus and ovaries in situ at the time of their LS diagnosis, 24 of 27 (88.9%) and 24 of 31 (77.4%) were aware of the option to undergo prophylactic hysterectomy and bilateral salpingo-oophorectomy (BSO), respectively. Since LS diagnosis, 9 of 27 (33.3%) and 10 of 31 (32.2%) have since undergone prophylactic hysterectomy and BSO, respectively. Of the 31 women still with uterus/ovaries in situ, 8 (25.8%) reported increased gynaecologic screening practices. Conclusions: Women with LS in British Columbia are knowledgeable and aware of their gynaecologic cancer risks and elect prophylactic surgery more often and gynaecologic screening less often than previously reported. Further research regarding patient satisfaction and a Canadian clinical practice guideline may assist with consistency of care and improving survivorship for women with LS throughout the country.
S74 l JUNE JOGC JUIN 2011
O-OV-BSC-FEL-001 ���������������������������������������������������������������������� INCREASED EXPRESSION OF C-TERMINAL BINDING PROTEIN-2 IN EPITHELIAL OVARIAN CARCINOMA T. May Harvard Medical School, Gynecologic Oncology- Brigham and Women’s Hospital, 25 Shattuck Street , Boston, Massachusetts, 02115, USA L. Barroilhet, J. Yang, M. Singh, W. Welch, S. Sugrue, R. Berkowitz, S. Ng Objectives: Ovarian cancer is the leading cause of mortality from gynecological malignancy despite advancements in novel therapeutics. Our group recently demonstrated that C-terminalbinding-protein-2 (CtBP2) is overexpressed in epithelial ovarian carcinoma and alters their response to histone-deacetylase-(HDAC)inhibitors. We designed a study aimed at examining the differential gene expression profiles between wild-type and CtBP2-knockdown cancer cell-lines to identify key pathways regulated by CtBP2. Study Methods: Reverse-transcribed-RNA from CtBP2-wild-type and knockdown cell-lines was hybridized to Affymetrix-Gene1.0-ST-Microarray. Differentially expressed genes were identified using D-Chip and SAM, and selected genes validated using qRT-PCR. Ingenuity protein pathways were analyzed and key interactions verified by co-immunoprecipitation-assays and immunofluorescence-microscopy. Protein expression levels were examined using immunohistochemistry (IHC) on 64 ovarian tissues and Western blot analysis on 15 ovarian cell-lines. Results: Gene expression analysis identified 89 gene signatures largely involved in DNA repair. A significant number of genes were down-regulated in the knockdown cell-lines, which is unexpected when CtBP2 is considered as a co-repressor. The nuclear protein Pinin was found to co-precipitate and co-localize with CtBP2 in the nucleus. IHC and Western-blot studies showed significant overexpression of Pinin in carcinoma compared to benign specimens (P<0.001). Conclusions: We propose CtBP2 is an ovarian cancer oncogene that regulates gene expression by modulating HDAC activity and DNA repair. Nuclear interaction between CtBP2 and the co-regulator protein Pinin was discovered suggesting that Pinin may modify the co-repressor function of CtBP2. Given that overexpression of CtBP2 decreases sensitivity of ovarian cancer to HDAC inhibitors, concurrent CtBP2 targeted therapy may enhance response of epithelial ovarian carcinoma to HDAC inhibitor therapy.
O-OV-BSC-MD-003 ����������������������������������������������������������������������� BRCA MUTATION AND METHYLATION STATUS DOES NOT CORRELATE WITH PROGNOSIS IN OVARIAN CANCER J. McAlpine University of British Columbia, Gynecologic oncology, F326 - 4500 Oak Street, Vancouver, BC, V6H 3V5, Canada H. Porter, S. Kalloger, J. Senz, C. Chow, K. Milne, J. Ding, L. Prentice, B. Nelson, D. Miller, D. Huntsman, C. Gilks Objectives: We characterized the clinical and molecular differences between HGS ovarian cancer with i) germline or somatic mutations in BRCA1/2, ii) methylation of BRCA1, and iii) normal BRCA1/2. Study Methods: 135 women underwent surgery for EOC with banked tissue and germline testing for BRCA1/2 mutations. Histopathology, germline and somatic BRCA1/2 mutations, BRCA1 methylation, and BRCA1/2 mRNA expression levels distinguished 4 subgroups. Results: 106 cases were HGS with 28 (26%) germline/somatic mutations (19% BRCA1, 7% BRCA2) (group 1), 21 (20%) methylation of BRCA1 (group 2), and 57 (54%) with no BRCA loss (group 3). Group 4 consisted of 29 cases of non-HGS. mRNA expression levels correlated with group (p=0.0011). Among HGS cancers, mutation carriers were younger (50.5y BRCA1, 54y BRCA2 vs. 63 yrs, p<0.0001), with no difference in stage, ascites,
ORAL PRESENTATIONS | EXPOSÉS
CA125 level, platinum sensitivity, cytoreduction rate, neoadjuvant, follow-up, or progression between groups. Kaplan-Meier survival analyses showed survival advantage only in the non-HGS (p=0.046). p53 abnormalities differed with complete absence or overexpression of p53 in essentially all BRCA 1/2 mutation and BRCA1 methylated cases (p=0.006). Expression of the immune marker TIA-1 was also significantly greater in Groups 1 and 2 (p=0.0048). Conclusions: Loss of BRCA function is a common event in HGS cancers (46%). p53 abnormalities and TIA-1 expression are more common in these cases. There was no survival advantage in cases with BRCA mutation or methylation. Cases without BRCA abnormality have as yet undetermined changes that are equivalent to BRCA loss in terms of response to chemotherapy and survival.
O-OV-CLI-FEL-003 ����������������������������������������������������������������������� TUBAL LIGATION AND RISK OF OVARIAN CARCINOMA SUBTYPES S. Salvador University of British Columbia, Gynaecologic Oncology, F326 - 4500 Oak Street, Vancouver, BC, V6H 3V5, Canada V. McGuire, A. Felberg, D. Miller, P. M. Webb, G. Chenevix-Trench, H. Risch, M. A. Rossing, J.A. Doherty, M.T. Goodman, G. Lurie, R.B. Ness, K. Moysich, J. Chang-Claude, R. Hein, S. Krüger Kjær, A. Jensen, E. Høgdall, R.T. Palmieri, J.M. Schildkraut, A. Berchuck , K.L. Terry, D.W. Cramer, E.V. Bandera, S.H. Olson, M.G. Williams-King, L. Rodriguez-Rodriguez, L.A. Kiemeney, T. Marees, L. F.A.G. Massuger, A.M. van Altena, C. L. Pearce, A.H. Wu, M.C. Pike, A.S. Whittemore, W. Sieh, on behalf of the Ovarian Cancer Association Consortium Objectives: Tubal ligation is protective for ovarian carcinoma. However, the effects of tubal ligation on subtype-specific risks and the influence of age at the time of the procedure are poorly understood. Study Methods: This study included 8338 invasive cases and 14,675 controls from fourteen case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). We used conditional logistic regression for pooled analyses, matched on site and age, and adjusted for race, duration of oral contraceptive use, and number of full-term births. There was little evidence of heterogeneity among sites (phet=0.32). Subtype-specific analyses were conducted for serous (n=4774), endometrioid (n=1318), clear cell (n=754), and mucinous (n=609) histotypes. High-grade (n=4446) and low-grade (n=328) serous carcinomas were defined by FIGO grades 2+ and 1, respectively. Results: Tubal ligation was associated with a 29% decreased risk (OR, 0.71; 95% CI, 0.66-0.77; p <0.001) of ovarian carcinoma overall. Furthermore, tubal ligation was consistently associated with decreased risks of all invasive histologic subtypes: high-grade serous (OR=0.81; 95% CI=0.73-0.88; p <0.001), low-grade serous (OR=0.82; 95% CI=0.59-1.14; p=0.23), endometrioid (OR=0.48; 95% CI=0.40-0.58; p <0.001), clear cell (OR=0.52; 95% CI=0.400.66; p <0.001) and mucinous (OR=0.61; 95% CI=0.48-0.80; p=0.002). Younger age at tubal ligation was not associated with greater protection from ovarian carcinoma overall or any specific subtype (ptrend >0.05). Conclusions: Our findings indicate that tubal ligation reduces the risk of all invasive ovarian carcinoma subtypes. Contrary to our expectation, the protective effects of tubal ligation did not diminish with age up to 50 years at the time of the procedure.
O-OV-HPOL-MD-001 ������������������������������������������������������������������� TEMPORAL TRENDS IN THE PROPORTION CURED AMONG WOMEN DIAGNOSED WITH OVARIAN CANCER IN CANADA 1992-2005: A POPULATION-BASED STUDY L. Elit
Juravinski Cancer Centre, Gynecologic Oncology, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada A. Lytwyn, N. Akhtar-Danesh Objectives: Ovarian cancer affects about 2600 women annually in Canada and about 1750 are expected to die from this disease. We used a model to determine whether age or regional factors affected patient outcome between 1992-2005. Study Methods: The cure fraction model was used to estimate proportion cured and relative survival pattern for uncured patients. Relative survival is defined as the observed survival among cancer patients divided by the expected survival in the general population. Cure fraction is the proportion of cancer patients who survived the disease and no longer experience the excess mortality rate. The cure fraction and the relative survival were estimated by age group and province. Results: 24,949 patients diagnosed with ovarian cancer (mean age at diagnosis 54.9 (SD=14.4) year) were included in this analysis. Cure fraction and relative survival substantially decreased with age. Cure fraction rate for the youngest group (< 30 years) was about 90% compared to about 18% in the oldest group (70-79 years). It was significantly lower in Ontario compared to the other provinces in Canada. Although the cure fraction did not increase over time, the median survival for the uncured patients increased. Conclusions: The findings indicate that although advancements in treatment did not increase the cure fraction rate, it increased the median survival. The lower cure fraction rate in Ontario may reflect variations in patient or process factors such as patterns of care and access to care.
O-VUL-BSC-MD-001 �������������������������������������������������������������������� EXPRESSION OF METASTASIS SUPPRESSOR GENE KAI1 IN MELANOMA OF THE FEMALE TRACT L. Gilbert McGill University, Obstetrics & Gynecology, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada C. Martins, K. Jardon, J. Arseneau, M. Burnier Objectives: Melanoma of the female tract is extremely rare but highly aggressive. Metastasis suppressor genes (MSGs) have been recognized by their decreased presence in metastatic cancer cells. KAI1 has been identified as an MSG that may promote tumor cell dormancy. It is believed that the expression of KAI1 is inversely correlated with the metastatic potential of numerous cancers. The aim of this study was to evaluate the immunohistochemical expression of KAI1 in sections of melanoma of the female tract and determine possible correlations with the development of metastatic disease. Study Methods: Six formalin-fixed paraffin-embedded human vulvar melanoma and three vaginal melanoma slides were immunostained in an automated machine with a mouse anti-human KAI1 antibody and compared with clinical data. Immunohistochemistry staining was assessed by assigning each case a score according to the percentage of stained cells. Results: The immunohistochemical results of KAI1 expression displayed staining 44 % of specimens. The results of the Fisher Exact test indicated that the absence of KAI1 expression was significantly associated with the development of metastatic disease (p=0.0476). Conclusions: To the best of our knowledge, this is the first time that KAI1 expression has been investigated in melanoma of the female tract. The absence of KAI1 expression is significantly correlated with metastatic disease. It suggests that KAI1 may represent a potential prognostic factor and that upregulation of KAI1 may be effective in preventing metastatic development in this particular tumor. Studies with larger samples are needed for further investigation.
JUNE JOGC JUIN 2011 l S75