- Email: [email protected]
Evaluation of preoperative imaging for low risk endometrial cancer patients
206
Abstracts / Gynecologic Oncology 139 (2015) 178–207
CK5+ tumors were also ER+). CK5 was expressed in 5/6 overall and 4/4 ER+ epithelial ovarian cancer cell lines ranging from 2.4–52.7% positive cells. CK5+ compared to CK5− cells were slower cycling. The prevalence of CK5+ cells increased following 48 hour cisplatin treatment in 4/5 cell lines tested. CK5+ compared to CK5− ovarian cancer cells were more resistant to cisplatin induced apoptosis. Conclusion: CK5 is expressed in a significant proportion of epithelial ovarian cancers and represents a slower cycling, chemoresistant subpopulation that may warrant co-targeting in combination therapy. Learning objective: Learners will be able to identify a subpopulation of cells in epithelial ovarian cancers that are therapy resistant that may demonstrate benefit from alternative combination therapy approaches. doi:10.1016/j.ygyno.2015.07.087
Oxidative stress and genetic variation in endometrial cancer E. Salinas, M. TenNapel, F. Domann, M. Goodheart. University of Iowa Hospitals and Clinics, Iowa City, IA, USA Objectives: It has been suggested that reactive oxygen species (ROS) contribute to the carcinogenic process. The effect of genetic variation with regards to ROS and response to oxidative stress within endometrial cancer is unclear. Our study aims to determine associations between oxidative stress related single nucleotide polymorphisms (SNPs) and endometrial cancer. This may in turn lead to the identification of biomarkers associated with the development of endometrial cancer. Methods: Genotyping was performed on 79 patients (58 with cancer, 21 without cancer) at 48 known SNPs using Fluidigm 192.24 Dynamic Array integrated fluid circuits (Fluidigm Incorporated, San Francisco, CA). Linear regression analysis was used to assess SNP-endometrial cancer incidence, grade and stage associations while controlling for patient characteristics. A chart review determined age, body mass index (BMI), grade, stage, histologic type, recurrence, and current disease status of patients with and without endometrial cancer. Univariate analysis determined age and BMI were associated with cancer incidence and included in the final model. Age and BMI were not associated with stage or grade and therefore not included in those models. Results: One SNP rs1042522 within TP53 was associated with cancer incidence (p b 0.05). The CC genotype demonstrated an increased risk of cancer development when compared to the GG genotype (p = 0.0096), OR = 10.56 (95% CI: 0.838, 133.1) while controlling for age and BMI. SNP rs2273773 within SIRT1 was associated with advanced stage disease. The TT genotype was associated with increased disease when compared to the CT genotype, OR = 9.0 (95% CI: 1.471, 55.1). Three SNPs located within FOXO3 were associated with increased cancer grade. FOXO3 SNP rs6911407 genotype CC (p = 0.015), SNP rs2802288 genotype GG (p = 0.011), and SNP rs9400239 genotype CC (p = 0.032) were all associated with higher grade than the other genotypes. Conclusion: Several oxidative stress related genes appear to be associated with endometrial cancer development, stage, and grade. These genes include TP53, SIRT1 and FOXO3. SNPs within these genes should be further investigated as potential biomarkers to identify patients at increased risk for endometrial cancer development. Learning objective: − Demonstrate a correlation between reactive oxygen species, response to oxidative stress, and endometrial cancer. –Examine the relationship between SNPs at candidate genes involved in oxidative stress pathways in patients with and without endometrial cancer. –Identify the importance of genetic biomarker discovery for patients at increased risk for cancer development. doi:10.1016/j.ygyno.2015.07.088
Geographic access to gynecologic cancer care in the United States D.I. Shalowitz, A.M. Vinograd, R.L.Giuntoli II. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Objectives: To identify regions of the United States with geographic barriers to access high-quality care for gynecologic malignancies. Methods: Geographic Information Systems (GIS) were used to identify United States counties farther than 50 miles from the closest gynecologic oncologist, and Hospital Referral Regions (HRRs) that do not contain the primary professional address of at least one gynecologic oncologist. U.S. Census data were used to analyze demographic characteristics of low-access counties. County-level cancer incidence was estimated using the Centers for Disease Control and Prevention’s State Cancer Profiles. Results: 36% (1125/3143) of counties are further than 50 miles from the nearest gynecologic oncologist. 14.8 million women live in lowaccess counties (LACs). Annually, approximately 7663 women with gynecologic cancers may experience geography-related disparities in access. Residents of LACs have lower median household income, are more likely to be White and/or Hispanic, and less likely to be Black. 40% (123/306) of HRRs do not contain the primary address of a gynecologic oncologist. Conclusion: Approximately 9% of the female population of the United States are likely to experience a geographic barrier to access high-quality care for gynecologic malignancies. Future investigations should assess whether residents of low-access counties in fact utilize high-quality care less often, and whether there is a resultant disparity in clinical outcomes. Learning objective: 1. Learners will be able to identify areas of the United States with low geographic access to gynecologic cancer care. 2. Learners will be able to identify key demographic characteristics of low-access US counties. 3. Learners will be able to identify the policy implications of disparities in access to high-quality gynecologic cancer care. doi:10.1016/j.ygyno.2015.07.089
Evaluation of preoperative imaging for low risk endometrial cancer patients A. Carrubba, B. Corr, J. Sheeder, S. Guntupalli. University of Colorado Anschutz Medical Campus, Aurora CO, USA Objectives: Current NCCN guidelines recommend preoperative thoracic imaging for all patients undergoing surgery for endometrial cancer. With the majority of patients being diagnosed and treated with stage I disease, the goal of this study was to evaluate the incidence of diagnosing pulmonary metastasis from preoperative imaging in a low risk patient population. Methods: A retrospective cross-sectional study of all patients undergoing surgical evaluation for endometrial cancer at a single institution from 2011 to 2014 was performed. Low risk patients were defined as having a preoperative pathology sample of grade I endometroid endometrial cancer and a physical exam that was not concerning for disease spread outside of the uterus. Results: A total of 259 patients were evaluated for endometrial cancer, of which 243 (94%) had preoperative thoracic imaging. 141/ 243 (58%) of patients with preoperative imaging were identified as low risk by our criteria. 5/141 (3.5%) patients had preoperative chest X-ray (CXR) concerning for pulmonary metastasis, but follow up computed tomography (CT) showed no evidence of nodules seen on CXR. No low risk patients (0/141; 95% CI 0–2.2%) were identified as having pulmonary metastasis. An overall incidence of pulmonary metastasis found on preoperative imaging was 1.2% (3/243; 95% CI 0.2–2.6%). All three patients had preoperative grade 3 disease. Two patients had carcinosarcoma and one had adenosquamous histology.
Abstracts / Gynecologic Oncology 139 (2015) 178–207
Conclusion: The risk of diagnosing pulmonary metastasis during preoperative imaging in a low risk population for endometrial cancer is low. However, the mortality associated with undiagnosed pulmonary metastases is sufficiently high to warrant evaluation with radiographic imaging. Learning objective: Learners will be able to identify a low risk population for having distant disease and evaluate if their practice warrants preoperative imaging on this population. doi:10.1016/j.ygyno.2015.07.090
The effect of delayed time to treatment on survival in women with locally advanced cervical cancer W. Robinson, L. Shamsnia, R. Regn, M. Pascal, W. Robinson IV. Tulane University School of Medicine, New Orleans, LA, USA Objectives: The purpose of this report is to analyze the effect of multiple system-based factors on the survival of women with locally advanced (stage IIB–IVA) cervical cancer. Also to compare systembased to demographic and other factors for survival in this population. Methods: 386 women diagnosed with locally advancer cervical cancer and treated with radiation therapy and cisplatin chemotherapy from 2010–2010 in a large, inner-city institution were evaluated for time from diagnosis to beginning treatment, total treatment time, year treated, demographics and Progression-Free (PFS) and Overall Survival (OS). This data was collected from appropriate Tumor registries and Medical Records. Statistical tests including KaplanMeier curves, ANOVA, and Chi-square were used to analyze the data. Results: Median time from diagnosis to beginning treatment was 32.5 days. (range 9–61) Median total treatment time was 61.1 days. (range 43–77) Longer times from diagnosis to treatment were associated with both decreased PFS and OS (p b 0.01). Total treatment time, treatment before 2006, age, ethnicity and histology were not associated with PFS or OS. Conclusion: PFS and OS in women with locally advanced cervical cancer is decreased in relation to delays in beginning radiation/ chemotherapy. The total treatment time was longer than nationally recommended standards, but no effect on survival was seen. Institutional programs to decrease time to treatment would be likely to improve survival and should be put in place. Learning objective: Learners will be able to compare PFS and OS to treatment times in women with cervical cancer treated with radiation/ chemotherapy, and to consider options for improving these outcomes.
Objectives: To report on the distinguishing features between twin pregnancy with complete hydatidiform mole (CHM&CF) and placental mesenchymal dysplasia (PMD). Methods: Clinical outcomes from three institutional cases were reviewed and interpreted in the setting of the available literature. Results: In our 3 cases, all patients were diagnosed antenatally as CHM&CF. The first patient was aged 37 and delivered a viable female at 34 weeks via Cesarean hysterectomy. Her β-hCG normalized 2 months after delivery and remained normal. The second patient was aged 30 and delivered a viable male via Cesarean section at 25 weeks for preeclampsia with severe features. Her β-hCG trended down and reached normal 5 months after delivery and has remained so for 6 months of follow-up. The third patient was aged 32 and delivered a viable female at 39 weeks vaginally. She had an uncomplicated pregnancy, and was found to have PMD on pathologic examination. On sonographic and gross inspection, the grapelike vesicles seen in PMD resemble molar pregnancy. For this reason, it may be hard to differentiate between PMD and CHM&CF on imaging alone. In cases of PMD, the pregnant woman is generally asymptomatic; and there does not appear to be an increased risk of pre-eclampsia. The levels of beta-HCG are normal to slightly elevated. Of note, PMD is associated in up to 23% of cases with Beckwith–Wiedemann syndrome, which is characterized by omphalocele, macroglossia, and macrosomia. Fetal growth restriction has also been reported. Thus, the primary complications seen in cases of PMD are fetal, with few maternal complications. CHM&CF almost always results in maternal symptoms, the most common of which are vaginal bleeding, hyperthyroidism, and pre-eclampsia. These symptoms may be severe enough to lead to indicated pregnancy termination. The uterus usually measures larger than dates and the β-hCG level is significantly elevated. The risk of persistent gestational trophoblastic disease (GTD) in these women ranges from 19.5–62.5%, which are usually cured with single agent methotrexate. All reported cases have gone into complete remission. The gestational age at time of pregnancy termination or delivery does not appear to be an independent risk factor for development of persistent GTD. Conclusion: CHM&CF and placental mesenchymal dysplasia appear similar on antenatal imaging; however, it is important to attempt differentiating between these two diagnoses in order to provide optimal patient counseling and care. Learning objective: Learners will be able to identify key differentiating factors between twin gestation with complete mole and placental mesenchymal dysplasia. This will allow them to provide more informed consultations for these similar-appearing disorders with very different clinical outcomes. doi:10.1016/j.ygyno.2015.07.092
doi:10.1016/j.ygyno.2015.07.091
Differentiating twin pregnancy with complete hydatidiform mole and placental mesenchymal dysplasia L. McNallya, S.M. Uedab, L. Chenb. aUniversity of California, San Francisco, School of Medicine and Stanford School of Medicine, Division of Gynecologic Oncology, USA, bUniversity of California, San Francisco, School of Medicine, Division of Gynecologic Oncology, USA
207
Abstracts / Gynecologic Oncology 139 (2015) 178–207
CK5+ tumors were also ER+). CK5 was expressed in 5/6 overall and 4/4 ER+ epithelial ovarian cancer cell lines ranging from 2.4–52.7% positive cells. CK5+ compared to CK5− cells were slower cycling. The prevalence of CK5+ cells increased following 48 hour cisplatin treatment in 4/5 cell lines tested. CK5+ compared to CK5− ovarian cancer cells were more resistant to cisplatin induced apoptosis. Conclusion: CK5 is expressed in a significant proportion of epithelial ovarian cancers and represents a slower cycling, chemoresistant subpopulation that may warrant co-targeting in combination therapy. Learning objective: Learners will be able to identify a subpopulation of cells in epithelial ovarian cancers that are therapy resistant that may demonstrate benefit from alternative combination therapy approaches. doi:10.1016/j.ygyno.2015.07.087
Oxidative stress and genetic variation in endometrial cancer E. Salinas, M. TenNapel, F. Domann, M. Goodheart. University of Iowa Hospitals and Clinics, Iowa City, IA, USA Objectives: It has been suggested that reactive oxygen species (ROS) contribute to the carcinogenic process. The effect of genetic variation with regards to ROS and response to oxidative stress within endometrial cancer is unclear. Our study aims to determine associations between oxidative stress related single nucleotide polymorphisms (SNPs) and endometrial cancer. This may in turn lead to the identification of biomarkers associated with the development of endometrial cancer. Methods: Genotyping was performed on 79 patients (58 with cancer, 21 without cancer) at 48 known SNPs using Fluidigm 192.24 Dynamic Array integrated fluid circuits (Fluidigm Incorporated, San Francisco, CA). Linear regression analysis was used to assess SNP-endometrial cancer incidence, grade and stage associations while controlling for patient characteristics. A chart review determined age, body mass index (BMI), grade, stage, histologic type, recurrence, and current disease status of patients with and without endometrial cancer. Univariate analysis determined age and BMI were associated with cancer incidence and included in the final model. Age and BMI were not associated with stage or grade and therefore not included in those models. Results: One SNP rs1042522 within TP53 was associated with cancer incidence (p b 0.05). The CC genotype demonstrated an increased risk of cancer development when compared to the GG genotype (p = 0.0096), OR = 10.56 (95% CI: 0.838, 133.1) while controlling for age and BMI. SNP rs2273773 within SIRT1 was associated with advanced stage disease. The TT genotype was associated with increased disease when compared to the CT genotype, OR = 9.0 (95% CI: 1.471, 55.1). Three SNPs located within FOXO3 were associated with increased cancer grade. FOXO3 SNP rs6911407 genotype CC (p = 0.015), SNP rs2802288 genotype GG (p = 0.011), and SNP rs9400239 genotype CC (p = 0.032) were all associated with higher grade than the other genotypes. Conclusion: Several oxidative stress related genes appear to be associated with endometrial cancer development, stage, and grade. These genes include TP53, SIRT1 and FOXO3. SNPs within these genes should be further investigated as potential biomarkers to identify patients at increased risk for endometrial cancer development. Learning objective: − Demonstrate a correlation between reactive oxygen species, response to oxidative stress, and endometrial cancer. –Examine the relationship between SNPs at candidate genes involved in oxidative stress pathways in patients with and without endometrial cancer. –Identify the importance of genetic biomarker discovery for patients at increased risk for cancer development. doi:10.1016/j.ygyno.2015.07.088
Geographic access to gynecologic cancer care in the United States D.I. Shalowitz, A.M. Vinograd, R.L.Giuntoli II. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Objectives: To identify regions of the United States with geographic barriers to access high-quality care for gynecologic malignancies. Methods: Geographic Information Systems (GIS) were used to identify United States counties farther than 50 miles from the closest gynecologic oncologist, and Hospital Referral Regions (HRRs) that do not contain the primary professional address of at least one gynecologic oncologist. U.S. Census data were used to analyze demographic characteristics of low-access counties. County-level cancer incidence was estimated using the Centers for Disease Control and Prevention’s State Cancer Profiles. Results: 36% (1125/3143) of counties are further than 50 miles from the nearest gynecologic oncologist. 14.8 million women live in lowaccess counties (LACs). Annually, approximately 7663 women with gynecologic cancers may experience geography-related disparities in access. Residents of LACs have lower median household income, are more likely to be White and/or Hispanic, and less likely to be Black. 40% (123/306) of HRRs do not contain the primary address of a gynecologic oncologist. Conclusion: Approximately 9% of the female population of the United States are likely to experience a geographic barrier to access high-quality care for gynecologic malignancies. Future investigations should assess whether residents of low-access counties in fact utilize high-quality care less often, and whether there is a resultant disparity in clinical outcomes. Learning objective: 1. Learners will be able to identify areas of the United States with low geographic access to gynecologic cancer care. 2. Learners will be able to identify key demographic characteristics of low-access US counties. 3. Learners will be able to identify the policy implications of disparities in access to high-quality gynecologic cancer care. doi:10.1016/j.ygyno.2015.07.089
Evaluation of preoperative imaging for low risk endometrial cancer patients A. Carrubba, B. Corr, J. Sheeder, S. Guntupalli. University of Colorado Anschutz Medical Campus, Aurora CO, USA Objectives: Current NCCN guidelines recommend preoperative thoracic imaging for all patients undergoing surgery for endometrial cancer. With the majority of patients being diagnosed and treated with stage I disease, the goal of this study was to evaluate the incidence of diagnosing pulmonary metastasis from preoperative imaging in a low risk patient population. Methods: A retrospective cross-sectional study of all patients undergoing surgical evaluation for endometrial cancer at a single institution from 2011 to 2014 was performed. Low risk patients were defined as having a preoperative pathology sample of grade I endometroid endometrial cancer and a physical exam that was not concerning for disease spread outside of the uterus. Results: A total of 259 patients were evaluated for endometrial cancer, of which 243 (94%) had preoperative thoracic imaging. 141/ 243 (58%) of patients with preoperative imaging were identified as low risk by our criteria. 5/141 (3.5%) patients had preoperative chest X-ray (CXR) concerning for pulmonary metastasis, but follow up computed tomography (CT) showed no evidence of nodules seen on CXR. No low risk patients (0/141; 95% CI 0–2.2%) were identified as having pulmonary metastasis. An overall incidence of pulmonary metastasis found on preoperative imaging was 1.2% (3/243; 95% CI 0.2–2.6%). All three patients had preoperative grade 3 disease. Two patients had carcinosarcoma and one had adenosquamous histology.
Abstracts / Gynecologic Oncology 139 (2015) 178–207
Conclusion: The risk of diagnosing pulmonary metastasis during preoperative imaging in a low risk population for endometrial cancer is low. However, the mortality associated with undiagnosed pulmonary metastases is sufficiently high to warrant evaluation with radiographic imaging. Learning objective: Learners will be able to identify a low risk population for having distant disease and evaluate if their practice warrants preoperative imaging on this population. doi:10.1016/j.ygyno.2015.07.090
The effect of delayed time to treatment on survival in women with locally advanced cervical cancer W. Robinson, L. Shamsnia, R. Regn, M. Pascal, W. Robinson IV. Tulane University School of Medicine, New Orleans, LA, USA Objectives: The purpose of this report is to analyze the effect of multiple system-based factors on the survival of women with locally advanced (stage IIB–IVA) cervical cancer. Also to compare systembased to demographic and other factors for survival in this population. Methods: 386 women diagnosed with locally advancer cervical cancer and treated with radiation therapy and cisplatin chemotherapy from 2010–2010 in a large, inner-city institution were evaluated for time from diagnosis to beginning treatment, total treatment time, year treated, demographics and Progression-Free (PFS) and Overall Survival (OS). This data was collected from appropriate Tumor registries and Medical Records. Statistical tests including KaplanMeier curves, ANOVA, and Chi-square were used to analyze the data. Results: Median time from diagnosis to beginning treatment was 32.5 days. (range 9–61) Median total treatment time was 61.1 days. (range 43–77) Longer times from diagnosis to treatment were associated with both decreased PFS and OS (p b 0.01). Total treatment time, treatment before 2006, age, ethnicity and histology were not associated with PFS or OS. Conclusion: PFS and OS in women with locally advanced cervical cancer is decreased in relation to delays in beginning radiation/ chemotherapy. The total treatment time was longer than nationally recommended standards, but no effect on survival was seen. Institutional programs to decrease time to treatment would be likely to improve survival and should be put in place. Learning objective: Learners will be able to compare PFS and OS to treatment times in women with cervical cancer treated with radiation/ chemotherapy, and to consider options for improving these outcomes.
Objectives: To report on the distinguishing features between twin pregnancy with complete hydatidiform mole (CHM&CF) and placental mesenchymal dysplasia (PMD). Methods: Clinical outcomes from three institutional cases were reviewed and interpreted in the setting of the available literature. Results: In our 3 cases, all patients were diagnosed antenatally as CHM&CF. The first patient was aged 37 and delivered a viable female at 34 weeks via Cesarean hysterectomy. Her β-hCG normalized 2 months after delivery and remained normal. The second patient was aged 30 and delivered a viable male via Cesarean section at 25 weeks for preeclampsia with severe features. Her β-hCG trended down and reached normal 5 months after delivery and has remained so for 6 months of follow-up. The third patient was aged 32 and delivered a viable female at 39 weeks vaginally. She had an uncomplicated pregnancy, and was found to have PMD on pathologic examination. On sonographic and gross inspection, the grapelike vesicles seen in PMD resemble molar pregnancy. For this reason, it may be hard to differentiate between PMD and CHM&CF on imaging alone. In cases of PMD, the pregnant woman is generally asymptomatic; and there does not appear to be an increased risk of pre-eclampsia. The levels of beta-HCG are normal to slightly elevated. Of note, PMD is associated in up to 23% of cases with Beckwith–Wiedemann syndrome, which is characterized by omphalocele, macroglossia, and macrosomia. Fetal growth restriction has also been reported. Thus, the primary complications seen in cases of PMD are fetal, with few maternal complications. CHM&CF almost always results in maternal symptoms, the most common of which are vaginal bleeding, hyperthyroidism, and pre-eclampsia. These symptoms may be severe enough to lead to indicated pregnancy termination. The uterus usually measures larger than dates and the β-hCG level is significantly elevated. The risk of persistent gestational trophoblastic disease (GTD) in these women ranges from 19.5–62.5%, which are usually cured with single agent methotrexate. All reported cases have gone into complete remission. The gestational age at time of pregnancy termination or delivery does not appear to be an independent risk factor for development of persistent GTD. Conclusion: CHM&CF and placental mesenchymal dysplasia appear similar on antenatal imaging; however, it is important to attempt differentiating between these two diagnoses in order to provide optimal patient counseling and care. Learning objective: Learners will be able to identify key differentiating factors between twin gestation with complete mole and placental mesenchymal dysplasia. This will allow them to provide more informed consultations for these similar-appearing disorders with very different clinical outcomes. doi:10.1016/j.ygyno.2015.07.092
doi:10.1016/j.ygyno.2015.07.091
Differentiating twin pregnancy with complete hydatidiform mole and placental mesenchymal dysplasia L. McNallya, S.M. Uedab, L. Chenb. aUniversity of California, San Francisco, School of Medicine and Stanford School of Medicine, Division of Gynecologic Oncology, USA, bUniversity of California, San Francisco, School of Medicine, Division of Gynecologic Oncology, USA
207