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Is endometrial cancer different in Asian American women?
Abstracts / Gynecologic Oncology 137 (2015) 92–179
157
concurrent surgery. There was no difference in operative time, blood loss, or surgical complications between the groups. One patient in the concurrent surgery group required vaginal brachytherapy postoperatively. SUI severity and bother scores improved in the concurrent surgery group. Conclusions: Treatment of SUI at the time of endometrial cancer diagnosis is feasible and is not associated with a delay in time to the operating room. All women desired a referral to a urogynecologist preoperatively and half opted for concurrent surgery. Concurrent treatment of SUI and endometrial cancer may affect quality of life, and further studies are warranted.
doi:10.1016/j.ygyno.2015.01.392
diabetics (HR 0.61; 95% CI 0.30, 1.23 for OS and HR 1.06; 95% CI 0.34, 3.30 for PFS). No difference was detected in PFS when comparing diabetics according to histologic subtype and metformin use (Figure). Conclusions: When risk-adjusted for differences in the prevalence of patient-, disease-, and treatment-specific covariates, OS was similar between diabetic and nondiabetic EC patients as well as between metformin users and nonusers or nondiabetics. Similar findings were observed for PFS.
doi:10.1016/j.ygyno.2015.01.391
389 — Poster Session Cancer of the uterus and treatment of incontinence (CUTI) K.M. Robisona, E. Lokichb, P.A. DiSilvestroa, S. Ramanb, C. Luisb, C. Rakera, M. Clarkc, K. Wohlrabb. aWomen and Infants Hospital, Brown University, Providence, RI, USA, bBrown University, Women and Infants Hospital, Providence, RI, USA, cBrown University, Providence, RI, USA Objectives: To determine if women with clinical stage I endometrial cancer can be effectively screened for stress urinary incontinence (SUI) by their gynecologic oncologist and referred to an urogynecologist for concurrent treatment of their endometrial cancer and SUI without a significant delay in their cancer surgery. Methods: Women presenting to a tertiary-care affiliated gynecologic oncology office with a diagnosis of clinical stage I endometrial cancer were screened for SUI with the question “Do you leak urine with lifting, coughing, or sneezing?”. Women who screened positive were offered referral to a urogynecologist. Baseline SUI severity and bother scores were collected with validated questionnaires. If the patient opted for urogynecology referral, further SUI testing was left up to the discretion of the urogynecologist. For patients who opted for concurrent surgical treatment, coordinated surgical time was scheduled. Results: A total of 59 women were screened for SUI and 23 women (39%) screened positive. Two women refused participation and one was ineligible. All 20 eligible women opted for referral to urogynecology and 9 (45%) opted for concurrent SUI and endometrial cancer surgery. There was no difference in tumor histology, grade, stage, or demographics between women choosing concurrent surgery and women choosing nonsurgical SUI management. The mean time to surgery for all women opting for a referral to urogynecology was 24.2 days compared to 20 days (P = 0.2) for women who screened negative for SUI. The mean time from initial oncology visit to surgery was 23.8 days for women who had concurrent cancer and SUI surgery compared to 24.8 days (P = 0.9) for women who declined
390 — Poster Session Magnetic resonance imaging utility to predict myometrial invasion in endometrial carcinoma: 10 years experience of single institution in Argentina J. Di Guilmi Sr. Hospital Britanico de Buenos Aires, Buenos Aires, Argentina Objectives: To determine the sensitivity and specificity of magnetic resonance imaging (MRI) in assessing myometrial invasion in patients with endometrial carcinoma compared with deferred biopsy. Methods: Clinical records of 87 patients diagnosed with endometrial carcinoma from April 2004 to October 2012 were investigated retrospectively to calculate sensitivity, specificity, and positive and negative likelihood ratio (PLR and NLR) of MRI compared to the gold standard of deferred biopsy. We also compared MRI and intraoperative frozen section to determine invasion concordance. Results: Eight-seven patients were analyzed between 2004 and 2012, resulting in a sensitivity of 71.4% (95% CI 0.48–0.89), specificity of 86.36% (95% CI 0.75–0.93), positive predictive value (PPV) of 62.5%, and negative predictive value (NPV) of 90.5%. The PLR was 5.2 and the NLR was 0.33. The absolute concordance between MRI and deferred biopsy was 82.8%. There was agreement between MRI and frozen section in 85.9% (kappa = 0.61) of the cases, while concordance between frozen section and deferred biopsy was 96.5%. Conclusions: MRI is a useful study to evaluate deep myometrial invasion, although it does not replace intraoperative biopsy. The study's safety, determined mostly by its high NPV, suggests its use as inclusion criteria in fertility-preserving treatment in young women. MRI also allows the calculation of operating room time for those patients with an estimated prolonged surgery.
doi:10.1016/j.ygyno.2015.01.393
391 — Poster Session Is endometrial cancer different in Asian American women? L.E. Dockerya, N.A. Connb, W.C. Strohsnittera, Y.B. Kimc, E. ChapmanDavisd. aTufts New England Medical Center, Boston, MA, USA, bTufts University School of Medicine, Boston, MA, USA, cTufts Medical Center, Boston, MA, USA, dTufts University School of Medicine, Tufts Medical Center, Boston, MA, USA Objectives: Asian Americans (AAs) represent the fastest growing population over the last decade, according to the 2010 United States census, but little is known about the characteristics of endometrial cancer in this group. This study sought to analyze the clinicopathologic characteristics and outcomes of AA women with endometrial cancer as compared to other ethnicities.
158
Abstracts / Gynecologic Oncology 137 (2015) 92–179
Methods: We performed a retrospective review of 454 patients diagnosed with endometrial cancer at Tufts Medical Center between January 1, 2003 and December 31, 2013. Demographics, clinicopathologic characteristics, treatments, and survival outcomes were analyzed and compared among ethnicities. Due to the large sample size of Caucasians (n = 380), a random number generator was used to select 100 Caucasian cases for analysis. Results: Of 158 patients in the analysis, 33 (20.9%) were AA, 25 (15.8%) were black (B), and 100 (63.3%) were Caucasian (C). A total of 54.5% (18/33) of the AA population spoke a Chinese dialect and were first-generation immigrants. The mean age at diagnosis; menopause status; and proportion with stage I disease, low-grade cancer, and endometrioid histology did not differ across ethnic groups. AAs were more likely to be nulliparous (P = 0.03), had significantly lower mean body mass index (BMI) than either of the other two groups (27.3 AA vs. 36 B, 36 C), and were less likely to be obese (19.4% vs. 68.4% B, 71.3% C; P b 0.0001). AAs and Bs both had a higher proportion of women with stages III–IV disease compared to Cs (28.1% AA, 32% B vs. 13% C; P = 0.04). There was no difference in the proportion of patients who received surgery, adjuvant chemotherapy, or radiation across ethnic groups. There was no difference in overall survival (OS) at 2 years across ethnic groups (86.5% AA, 85.0% B, 90.6% C; P = 0.88). After adjusting for age, stage, and histology, there was no difference in OS (Table 1). Conclusions: AA women are more likely to present with advancedstage disease but otherwise have similar clinicopathologic characteristics and outcomes to other ethnicities. The proportion with type I endometrial cancer was similar to other ethnicities despite lower mean BMI and rate of obesity. This suggests that AA women are at risk for type I endometrial cancer at a much lower BMI threshold compared to other ethnicities.
volumes were assessed. Xenograft tumors were harvested from untreated animals as well as both treatment arms at the point of NVP BKM-120 sensitivity, and RNA was extracted from each fresh tumor (n = 23). Genome-level changes were assessed using the nextgeneration Illumina HiSEQ 2000 platform. Controlling for changes in the vehicle tumors, significant gene changes that occurred exclusively as a xenograft tumor transitioned from being NVP BKM-120sensitive to -resistant were identified and stratified by the number of gene–gene interactions, number of initiating molecules, and known interactions with AKT. To further understand the biological meaning of resistance, we performed pattern, functional, and pathways analyses. Results: A 54-gene expression signature was identified consisting of genes that significantly changed with the development of sensitivity and subsequent resistance. This signature demonstrated significant counterregulation at the time of resistance. Sensitivity to PI3K inhibition
Table 1 Survival (proportional hazard). Race
HRcrude (95% CI)
p
HRadj (95% CI)
p
Asian Black Caucasian
1.21 (.52, 2.78) 1.20 (.44, 3.24) 1.0 ref
.66 .72
1.05 (.43, 2.54) .84 (.29, 2.43) 1.0 ref
.92 .75
doi:10.1016/j.ygyno.2015.01.394
392 — Poster Session Next-generation sequencing demonstrates genomic signature of resistance patterns following phosphatidylinositol 3-kinase (PI3K) inhibition J.A. Rauh-Haina, M. Kimb, L. Zhangb, R. Fosterb, B.R. Ruedab, M. Bhasinc, W.B. Growdona. aMassachusetts General Hospital, Harvard University, Boston, MA, USA, bMassachusetts General Hospital, Boston, MA, USA, cBeth Israel Deaconess Medical Center, Boston, MA, USA Objectives: Inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway is a promising therapeutic avenue for women with endometrial cancer, given the high prevalence of innate PI3K pathway activation. In early-phase trials, response to these therapies has been of limited duration, and the objective of this investigation was to utilize a novel model to understand the genomic changes associated with resistance to PI3K inhibition. Methods: With institutional review board approval, NOD/SCID mice bearing xenografts derived from a primary endometrioid endometrial human tumor (ENCA1) were divided into a two-arm cohort (n = 12/arm) with equivalent tumor volumes. The arms received either NVP BKM-120 (30 mg/kg) or vehicle, and xenograft tumor
was associated with marked alteration in gene sets involved with cell death and survival, inflammatory response, cell-to-cell signaling, cellular movement, and immune cell traffic. Resistance to NVP BKM120 led to significant shifts in additional genes involved in cell migration/invasion and lipid metabolism. Conclusions: These results suggest that resistance to PI3K inhibition with NVP BKM-120 is a multifactorial process governed by several sets of genetic events in specific molecular pathways. Further validation of individual pathways and genes will be crucial to uncoupling PI3K resistance.
doi:10.1016/j.ygyno.2015.01.395
393 — Poster Session Does obesity affect pathologic agreement of initial and final tumor grade of disease in endometrial cancer patients? L.R. Daily, J.D. Boone, H.C. Machemehl, E.D. Thomas, G. McGwin, M. Straughn, C.A. Leath III. University of Alabama at Birmingham, Birmingham, AL, USA Objectives: Various staging strategies are used in the management of endometrial cancer (EC), including intraoperative frozen section, triage based on preoperative biopsy results, and sentinel node biopsy. The objective of this study was to compare preoperative and postoperative tumor grade to determine if surgical staging based on preoperative grade is a feasible approach and whether the level of agreement is affected by obesity.
157
concurrent surgery. There was no difference in operative time, blood loss, or surgical complications between the groups. One patient in the concurrent surgery group required vaginal brachytherapy postoperatively. SUI severity and bother scores improved in the concurrent surgery group. Conclusions: Treatment of SUI at the time of endometrial cancer diagnosis is feasible and is not associated with a delay in time to the operating room. All women desired a referral to a urogynecologist preoperatively and half opted for concurrent surgery. Concurrent treatment of SUI and endometrial cancer may affect quality of life, and further studies are warranted.
doi:10.1016/j.ygyno.2015.01.392
diabetics (HR 0.61; 95% CI 0.30, 1.23 for OS and HR 1.06; 95% CI 0.34, 3.30 for PFS). No difference was detected in PFS when comparing diabetics according to histologic subtype and metformin use (Figure). Conclusions: When risk-adjusted for differences in the prevalence of patient-, disease-, and treatment-specific covariates, OS was similar between diabetic and nondiabetic EC patients as well as between metformin users and nonusers or nondiabetics. Similar findings were observed for PFS.
doi:10.1016/j.ygyno.2015.01.391
389 — Poster Session Cancer of the uterus and treatment of incontinence (CUTI) K.M. Robisona, E. Lokichb, P.A. DiSilvestroa, S. Ramanb, C. Luisb, C. Rakera, M. Clarkc, K. Wohlrabb. aWomen and Infants Hospital, Brown University, Providence, RI, USA, bBrown University, Women and Infants Hospital, Providence, RI, USA, cBrown University, Providence, RI, USA Objectives: To determine if women with clinical stage I endometrial cancer can be effectively screened for stress urinary incontinence (SUI) by their gynecologic oncologist and referred to an urogynecologist for concurrent treatment of their endometrial cancer and SUI without a significant delay in their cancer surgery. Methods: Women presenting to a tertiary-care affiliated gynecologic oncology office with a diagnosis of clinical stage I endometrial cancer were screened for SUI with the question “Do you leak urine with lifting, coughing, or sneezing?”. Women who screened positive were offered referral to a urogynecologist. Baseline SUI severity and bother scores were collected with validated questionnaires. If the patient opted for urogynecology referral, further SUI testing was left up to the discretion of the urogynecologist. For patients who opted for concurrent surgical treatment, coordinated surgical time was scheduled. Results: A total of 59 women were screened for SUI and 23 women (39%) screened positive. Two women refused participation and one was ineligible. All 20 eligible women opted for referral to urogynecology and 9 (45%) opted for concurrent SUI and endometrial cancer surgery. There was no difference in tumor histology, grade, stage, or demographics between women choosing concurrent surgery and women choosing nonsurgical SUI management. The mean time to surgery for all women opting for a referral to urogynecology was 24.2 days compared to 20 days (P = 0.2) for women who screened negative for SUI. The mean time from initial oncology visit to surgery was 23.8 days for women who had concurrent cancer and SUI surgery compared to 24.8 days (P = 0.9) for women who declined
390 — Poster Session Magnetic resonance imaging utility to predict myometrial invasion in endometrial carcinoma: 10 years experience of single institution in Argentina J. Di Guilmi Sr. Hospital Britanico de Buenos Aires, Buenos Aires, Argentina Objectives: To determine the sensitivity and specificity of magnetic resonance imaging (MRI) in assessing myometrial invasion in patients with endometrial carcinoma compared with deferred biopsy. Methods: Clinical records of 87 patients diagnosed with endometrial carcinoma from April 2004 to October 2012 were investigated retrospectively to calculate sensitivity, specificity, and positive and negative likelihood ratio (PLR and NLR) of MRI compared to the gold standard of deferred biopsy. We also compared MRI and intraoperative frozen section to determine invasion concordance. Results: Eight-seven patients were analyzed between 2004 and 2012, resulting in a sensitivity of 71.4% (95% CI 0.48–0.89), specificity of 86.36% (95% CI 0.75–0.93), positive predictive value (PPV) of 62.5%, and negative predictive value (NPV) of 90.5%. The PLR was 5.2 and the NLR was 0.33. The absolute concordance between MRI and deferred biopsy was 82.8%. There was agreement between MRI and frozen section in 85.9% (kappa = 0.61) of the cases, while concordance between frozen section and deferred biopsy was 96.5%. Conclusions: MRI is a useful study to evaluate deep myometrial invasion, although it does not replace intraoperative biopsy. The study's safety, determined mostly by its high NPV, suggests its use as inclusion criteria in fertility-preserving treatment in young women. MRI also allows the calculation of operating room time for those patients with an estimated prolonged surgery.
doi:10.1016/j.ygyno.2015.01.393
391 — Poster Session Is endometrial cancer different in Asian American women? L.E. Dockerya, N.A. Connb, W.C. Strohsnittera, Y.B. Kimc, E. ChapmanDavisd. aTufts New England Medical Center, Boston, MA, USA, bTufts University School of Medicine, Boston, MA, USA, cTufts Medical Center, Boston, MA, USA, dTufts University School of Medicine, Tufts Medical Center, Boston, MA, USA Objectives: Asian Americans (AAs) represent the fastest growing population over the last decade, according to the 2010 United States census, but little is known about the characteristics of endometrial cancer in this group. This study sought to analyze the clinicopathologic characteristics and outcomes of AA women with endometrial cancer as compared to other ethnicities.
158
Abstracts / Gynecologic Oncology 137 (2015) 92–179
Methods: We performed a retrospective review of 454 patients diagnosed with endometrial cancer at Tufts Medical Center between January 1, 2003 and December 31, 2013. Demographics, clinicopathologic characteristics, treatments, and survival outcomes were analyzed and compared among ethnicities. Due to the large sample size of Caucasians (n = 380), a random number generator was used to select 100 Caucasian cases for analysis. Results: Of 158 patients in the analysis, 33 (20.9%) were AA, 25 (15.8%) were black (B), and 100 (63.3%) were Caucasian (C). A total of 54.5% (18/33) of the AA population spoke a Chinese dialect and were first-generation immigrants. The mean age at diagnosis; menopause status; and proportion with stage I disease, low-grade cancer, and endometrioid histology did not differ across ethnic groups. AAs were more likely to be nulliparous (P = 0.03), had significantly lower mean body mass index (BMI) than either of the other two groups (27.3 AA vs. 36 B, 36 C), and were less likely to be obese (19.4% vs. 68.4% B, 71.3% C; P b 0.0001). AAs and Bs both had a higher proportion of women with stages III–IV disease compared to Cs (28.1% AA, 32% B vs. 13% C; P = 0.04). There was no difference in the proportion of patients who received surgery, adjuvant chemotherapy, or radiation across ethnic groups. There was no difference in overall survival (OS) at 2 years across ethnic groups (86.5% AA, 85.0% B, 90.6% C; P = 0.88). After adjusting for age, stage, and histology, there was no difference in OS (Table 1). Conclusions: AA women are more likely to present with advancedstage disease but otherwise have similar clinicopathologic characteristics and outcomes to other ethnicities. The proportion with type I endometrial cancer was similar to other ethnicities despite lower mean BMI and rate of obesity. This suggests that AA women are at risk for type I endometrial cancer at a much lower BMI threshold compared to other ethnicities.
volumes were assessed. Xenograft tumors were harvested from untreated animals as well as both treatment arms at the point of NVP BKM-120 sensitivity, and RNA was extracted from each fresh tumor (n = 23). Genome-level changes were assessed using the nextgeneration Illumina HiSEQ 2000 platform. Controlling for changes in the vehicle tumors, significant gene changes that occurred exclusively as a xenograft tumor transitioned from being NVP BKM-120sensitive to -resistant were identified and stratified by the number of gene–gene interactions, number of initiating molecules, and known interactions with AKT. To further understand the biological meaning of resistance, we performed pattern, functional, and pathways analyses. Results: A 54-gene expression signature was identified consisting of genes that significantly changed with the development of sensitivity and subsequent resistance. This signature demonstrated significant counterregulation at the time of resistance. Sensitivity to PI3K inhibition
Table 1 Survival (proportional hazard). Race
HRcrude (95% CI)
p
HRadj (95% CI)
p
Asian Black Caucasian
1.21 (.52, 2.78) 1.20 (.44, 3.24) 1.0 ref
.66 .72
1.05 (.43, 2.54) .84 (.29, 2.43) 1.0 ref
.92 .75
doi:10.1016/j.ygyno.2015.01.394
392 — Poster Session Next-generation sequencing demonstrates genomic signature of resistance patterns following phosphatidylinositol 3-kinase (PI3K) inhibition J.A. Rauh-Haina, M. Kimb, L. Zhangb, R. Fosterb, B.R. Ruedab, M. Bhasinc, W.B. Growdona. aMassachusetts General Hospital, Harvard University, Boston, MA, USA, bMassachusetts General Hospital, Boston, MA, USA, cBeth Israel Deaconess Medical Center, Boston, MA, USA Objectives: Inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway is a promising therapeutic avenue for women with endometrial cancer, given the high prevalence of innate PI3K pathway activation. In early-phase trials, response to these therapies has been of limited duration, and the objective of this investigation was to utilize a novel model to understand the genomic changes associated with resistance to PI3K inhibition. Methods: With institutional review board approval, NOD/SCID mice bearing xenografts derived from a primary endometrioid endometrial human tumor (ENCA1) were divided into a two-arm cohort (n = 12/arm) with equivalent tumor volumes. The arms received either NVP BKM-120 (30 mg/kg) or vehicle, and xenograft tumor
was associated with marked alteration in gene sets involved with cell death and survival, inflammatory response, cell-to-cell signaling, cellular movement, and immune cell traffic. Resistance to NVP BKM120 led to significant shifts in additional genes involved in cell migration/invasion and lipid metabolism. Conclusions: These results suggest that resistance to PI3K inhibition with NVP BKM-120 is a multifactorial process governed by several sets of genetic events in specific molecular pathways. Further validation of individual pathways and genes will be crucial to uncoupling PI3K resistance.
doi:10.1016/j.ygyno.2015.01.395
393 — Poster Session Does obesity affect pathologic agreement of initial and final tumor grade of disease in endometrial cancer patients? L.R. Daily, J.D. Boone, H.C. Machemehl, E.D. Thomas, G. McGwin, M. Straughn, C.A. Leath III. University of Alabama at Birmingham, Birmingham, AL, USA Objectives: Various staging strategies are used in the management of endometrial cancer (EC), including intraoperative frozen section, triage based on preoperative biopsy results, and sentinel node biopsy. The objective of this study was to compare preoperative and postoperative tumor grade to determine if surgical staging based on preoperative grade is a feasible approach and whether the level of agreement is affected by obesity.