- Email: [email protected]
Trends in robotic surgery for endometrial cancer and the impact of hospital surgical volume on perioperative complications
Abstracts / Gynecologic Oncology 141 (2016) 2–208
155
374 – Poster Impact of carcinoma involving adenomyosis on the survival of patients with endometrial endometrioid adenocarcinoma B. Schlappe, J.A. Ducie, A.G.Z. Eriksson, R.A. Soslow, Y. Sonoda, K. Alektiar, N.R. Abu-Rustum, M.M. Leitao. Memorial Sloan Kettering Cancer Center, New York, NY, USA
doi:10.1016/j.ygyno.2016.04.403
Objectives: Data are conflicting regarding the effect of the presence of adenomyosis on the prognosis of endometrial cancer patients. The prognostic value of adenocarcinoma colonizing adenomyosis has not been evaluated. We assessed the effect of both the presence of adenomyosis and carcinoma-colonizing adenomyosis on the outcome of patients with endometrial endometrioid adenocarcinoma (EEAC) in a large single institution cohort. Methods: All patients who had primary surgical treatment of EEAC from 2000 to 2012 were identified from an institutional database. All pathology reports were reviewed by expert gynecologic pathologists. Adenocarcinoma involving adenomyosis did not influence reported depth of myometrial invasion. Relevant patient, clinical, and pathologic characteristics were collected, including the presence of adenomyosis in the hysterectomy specimen and the involvement of adenomyosis by endometrial adenocarcinoma. Appropriate statistical tests were used. Results: Query of the available database identified 1,751 eligible patients. The median age at diagnosis was 60 (range, 25–92 years). The majority of tumors were grade 1 (n = 1,076, 62%) and stage I (n = 1,491, 85%). Adenomyosis was present in 808 cases (46%) and carcinoma was found to involve adenomyosis in 114 cases (114/808, 14%). Cases without adenomyosis were found to have deeper myometrial invasion (P b .001) and those patients had a lower body mass index (P = .018). Median follow-up was 57 months (range, 0–183 months). Median overall survival for the entire cohort was not reached. Five-year overall survival for those with and without adenomyosis was 94% and 90%, respectively (P = .008). After controlling for stage and grade, however, the presence of adenomyosis was not associated with improved survival (HR 1.1, 95% CI 0.8–1.5). Within the adenomyosis group, there was no difference in overall survival (P = .54), disease-specific survival (P = .61), or recurrencefree survival (P = .84) when carcinoma involved adenomyosis. Conclusions: After controlling for other known prognostic factors, the presence of adenomyosis is not associated with survival in patients with endometrioid adenocarcinoma of the uterus. Adenocarcinoma involving adenomyosis does not alter the prognosis in patients with endometrial adenocarcinoma.
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Objectives: Lynch syndrome (LS) confers hereditary predisposition to multiple tumors. The incidence of endometrial cancer (EC) can match colorectal carcinoma, with a risk of up to 60%. The frequency of germline mutations of mismatch repair protein (MMR-P) in unselected patients with EC is 1.8% to 2.1%. Our objective was to analyze the expression of MMR-P (MLH1, MSH2, MSH6, and PMS2) with immunohistochemistry (IHC) in tumor tissue of unselected patients with EC at our institution, and describe morphologic features associated with altered expression of MMR-P. Methods: We enrolled 84 patients with EC who were treated at the Hospital Italiano at Buenos Aires, Argentina, between April 2014 and August 2015. IHC for MLH1, MSH2, MSH6, and PMS2 was performed using the Ventana Benchmark XT system. The following variables were analyzed: expression of MMR-P, age, Lynch-associated morphologic characteristics, and tumor stage at diagnosis. Results: The mean age of our population was 64.7 years (standard deviation 12.45), 12 patients (14.5%) were younger than 50 years. Twenty-eight patients had altered expression of at least 1 MMR-P (33.3%). Twenty-one patients (75%) had a deficit of MLH1/PMS2, 2 of PMS2 (7%), 1 of MSH2/MSH6 (4%), and 4 of MSH6 (14%). Among the patients with altered IHC, only 2 were younger than 50 years. Regarding histologic subtypes, there were 24 (86%) endometrioid carcinomas, 1 clear cell carcinoma, 1 serous carcinoma, and 2 undifferentiated carcinomas. The mean body mass index was 31. We performed a complete morphologic study of 26 surgical specimens. In 17 cases (65%), we found at least 1 characteristic associated with altered expression of MMR-P (TM-MMR-P). One patient in the subset that did not show TMMMR-P features and one other met clinical criteria for LS. Of the 28 patients with altered expression, 25 were surgically treated at our hospital. FIGO stage distribution was as follows: 56% stage IA, 24% stage IB, and 20% stage III. Conclusions: The deficit of expression of MMR-P is consistent with that reported in the literature. Preliminary results in our population might support the routine use of IHC in selected patients with EC. Further comparative studies are needed to define elements of suspicion for LS in these patients.
RO
372 – Poster Endometrial cancer and Lynch syndrome: Immunohistochemical characterization of endometrial cancer associated with changes in mismatch repair protein expression M.C. Riggi, A. Wernicke, G. Salvo, G.T. Saraniti, J.P. Santino, M.C. Saez, C.A. Vaccaro, M. Perrotta. Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
OF
TOV112D-Scr (IC50:6.5 μM), SKOV3-ip-Scr (IC50: 8 μM), and A2780CP70-Scr (IC50: 88 μM). Conclusions: MYB is overexpressed in OC and demonstrates altered growth, malignant behavior, and chemoresistance of OC. These data provide the first experimental evidence for a functional role of the novel MYB oncogene in OC.
doi:10.1016/j.ygyno.2016.04.404
373 – Poster Locally advanced cervical squamous cell carcinoma (CSCC): Impact of the FDG PET/CT in the primary staging Withdrawn at author’s request doi:10.1016/j.ygyno.2016.04.405
doi:10.1016/j.ygyno.2016.04.406
375 – Poster Trends in robotic surgery for endometrial cancer and the impact of hospital surgical volume on perioperative complications M.S. Guya, J. Sheederb, E.L. Eisenhauera, T.J. Reidc, S.R. Guntupallib. a University of Cincinnati, UC Health Medical Arts Building, Cincinnati, OH, USA, bUniversity of Colorado Denver, Aurora, CO, USA, cUniversity of Cincinnati, Cincinnati, OH, USA Objectives: We examine 5-year trends in robotic surgery for endometrial cancer and evaluate the impact of hospital robotic volume on surgical outcomes. Methods: Using the Healthcare Cost and Utilization Project National (Nationwide) Inpatient Sample (HCUP-NIS) Database from 2008 to 2012, patients who underwent robotic surgery for endometrial cancer were identified. Surgical (intraoperative and perioperative) complications were abstracted. Medical comorbidity scores were calculated using the Charlson comorbidity index (CCI). High-volume
Abstracts / Gynecologic Oncology 141 (2016) 2–208
achieved in ARK1 cells genetically by silencing AXL with shRNA (P = .0131) or therapeutically by selective inhibition of AXL with R428 in combination with paclitaxel (P = .0036). The novel delivery system, p5RHH, conjugated to siAXL, was shown to inactivate AXL in ARK1 cells at the RNA and protein level to a similar extent as traditional transfection technique (8.4-fold vs 8.7-fold decrease for RNA, respectively; 67% vs 83% knockdown at 48 hours and 84% vs 97% knockdown at 96 hours for protein, respectively). Conclusions: AXL expression is associated with chemoresistance in ovarian and uterine cell lines. Genetic inactivation of AXL or targeted therapy using R428 in taxane-resistant uterine cells reverses chemoresistance. To find a targeted therapy to mimic this genetic inactivation, both a novel AXL kinase inhibitor and a novel siRNA nano-particle delivery system were successfully used.
OF
doi:10.1016/j.ygyno.2016.04.408
377 – Poster Preparing for a paradigm shift in the treatment of ovarian cancer: Effect of online CME on oncologists' knowledge and competence T. Herrmanna, S. Pearcea, M. Millera, D.S. Dizonb. aMedscape Education, New York, NY, USA, bMassachusetts General Hospital/Harvard University, Boston, MA, USA Objectives: We sought to determine the effect of online continuing medical education on the knowledge and competence of oncologists regarding the use of poly ADP ribose polymerase (PARP) inhibitors in ovarian cancer. Methods: The effect of 2 educational interventions on the role of PARP inhibition in the treatment of ovarian cancer was analyzed to determine efficacy of online education. The activities launched online in August 2014 and April 2015, and data were collected through November 2014 and May 2015, respectively. The effects of education were assessed by comparing the same group of participants’ responses to knowledge- and case-based matched pre- postassessments. A paired 2-tailed t test was used to assess whether the mean postassessment score was different from the mean preassessment score. The McNemar χ2 statistic was used to measure changes in responses to individual questions. The effect size was calculated with the Cohen d. Results: A total of 151 oncologist responses during the study period were included in this outcomes analysis. Significant improvements in the knowledge of the rationale for targeting PARP inhibition and its link to synthetic lethality were seen as a result of participation in video lecture (n = 62, large effect d = 1.287, P b .05) and case-based roundtable (n = 91, large effect d = 1.352, P b .05). After participation, 44% were more likely to recognize that all patients with ovarian cancer should be tested for BRCA mutations (P b .05), 27% were more likely to correctly counsel appropriate patients on the potential efficacy of PARP inhibitors in the management of their disease (P b .05), and 33% were more likely to identify the correlation among BRCA mutations, PARP inhibitors, and overall survival as reported in the literature. In a patient with ovarian cancer whose disease was BRCA wild-type, more oncologists were able to identify the potential clinical efficacy of combining a PARP inhibitor with vascular endothelial growth factor blockade in this patient population (P b .05). Conclusions: This study demonstrates the effectiveness of online education that uses multiple formats and reinforces prior learning on improving knowledge and competence of oncologists regarding the use of PARP inhibitors in the management of ovarian cancer. Additional studies are needed to assess whether improved knowledge and competence translate to clinical practice.
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centers were defined as hospitals that completed more cases than the median for each year in the dataset. We compared patient characteristics, procedures, and outcomes, and examined trends over the 5-year period. A multivariable analysis (MVA) was completed to identify independent predictors of surgical complications in the robotic cohort. Results: A total of 7,066 patients were identified. Over the study period, rates of obesity increased (P b .001) as well as the CCI (P = .001). Lymph node dissection was less commonly performed (P b .001). Surgery volume increased in small or medium-sized (P b .001), private (P b .001), and teaching (P b0.001) hospitals. High-volume centers were more likely to be large (74% vs 62%, P b .001), teaching hospitals (78% vs 58%, P b .001), located in the northeastern or western United States, and were less likely to be privately owned (22% vs 31%, P b .001). Patients treated at highvolume centers were similar in age (P = .11), but had higher CCI values (2.5 ± 0.9 vs 2.6 ± 1.2, P = .002) and were more likely to undergo lymph node dissection (73% vs 68%, P = .007). MVA models included age, race, CCI, obesity, lymph node dissection, hospital size, ownership, teaching status, location, and volume. Increasing age (adjusted odds ratio [aOR] 1.02; 95% CI 1.02–1.03), CCI (aOR 1.25, 95% CI 1.18–1.33), obesity (aOR 1.50, 95% CI 1.30–1.73), and teaching hospital (aOR 1.23, 95% CI 1.05–1.45) independently predicted having a surgical complication. Large (aOR 0.85, 95% CI 0.74–0.99) or high-volume (aOR 0.81, 95% CI 0.66–0.98) hospital and Caucasian race (aOR 0.84, 95% CI 0.71–0.99) were associated with lower risk of complication. With increasing year of the procedure, patients were less likely to have a surgical complication (aOR 0.86, 95% CI 0.81–0.91). Conclusions: The strongest independent predictor of improved intraoperative and perioperative outcomes in robotic surgery for endometrial cancer is having surgery at a high-volume center.
RO
156
doi:10.1016/j.ygyno.2016.04.407
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376 – Poster AXL, a receptor tyrosine kinase, mediates platinum and taxane resistance in ovarian and uterine cancer M. Palisoul, M. Nguyen, H. Pan, A. Lohrey, R. Desai, S. Wickline, M.A. Powell, D.G. Mutch, K.C. Fuh. Washington University School of Medicine in St. Louis, St. Louis, MO, USA
UN
CO
Objectives: Expression of AXL is associated with a worse prognosis in ovarian cancer. We investigated the role of AXL expression in chemotherapy response in ovarian and uterine cancers, and sought to reverse chemoresistance through inactivation of AXL. Methods: In vitro cell viability (XTT) assays were performed to confirm response to chemotherapy in SKOV3-S/R (platinum sensitive/ resistant ovarian cell lines), OVCAR3/TP (taxane sensitive/resistant ovarian cell lines), and AN3CA/ARK1 (taxane sensitive/resistant uterine cell lines), and Western blotting was performed for AXL expression. XTT assays of ARK1 cells for paclitaxel resistance with AXL silencing by shRNA were performed. This was then repeated with selective small molecule inhibition of AXL with R428. AXL knockdown by siRNA was performed with either a traditional transfection reagent (DharmaFECT) or with a novel serum-stable, cell-penetrating, endosomolytic amphipathic peptide delivery system (p5RHH). Cell viability assays were analyzed using paired t tests. P b .05 was considered statistically significant. Results: Chemoresistance was validated with XTT assays for SKOV3S/R, OVCAR3/TP, AN3CA/ARK1 (P = .0666, P = .0005, P b .0001, respectively). Western blotting confirmed overexpression of AXL in chemoresistant cell lines, and lack of AXL expression in their chemosensitive counterparts. Reversal of paclitaxel resistance was
doi:10.1016/j.ygyno.2016.04.409
155
374 – Poster Impact of carcinoma involving adenomyosis on the survival of patients with endometrial endometrioid adenocarcinoma B. Schlappe, J.A. Ducie, A.G.Z. Eriksson, R.A. Soslow, Y. Sonoda, K. Alektiar, N.R. Abu-Rustum, M.M. Leitao. Memorial Sloan Kettering Cancer Center, New York, NY, USA
doi:10.1016/j.ygyno.2016.04.403
Objectives: Data are conflicting regarding the effect of the presence of adenomyosis on the prognosis of endometrial cancer patients. The prognostic value of adenocarcinoma colonizing adenomyosis has not been evaluated. We assessed the effect of both the presence of adenomyosis and carcinoma-colonizing adenomyosis on the outcome of patients with endometrial endometrioid adenocarcinoma (EEAC) in a large single institution cohort. Methods: All patients who had primary surgical treatment of EEAC from 2000 to 2012 were identified from an institutional database. All pathology reports were reviewed by expert gynecologic pathologists. Adenocarcinoma involving adenomyosis did not influence reported depth of myometrial invasion. Relevant patient, clinical, and pathologic characteristics were collected, including the presence of adenomyosis in the hysterectomy specimen and the involvement of adenomyosis by endometrial adenocarcinoma. Appropriate statistical tests were used. Results: Query of the available database identified 1,751 eligible patients. The median age at diagnosis was 60 (range, 25–92 years). The majority of tumors were grade 1 (n = 1,076, 62%) and stage I (n = 1,491, 85%). Adenomyosis was present in 808 cases (46%) and carcinoma was found to involve adenomyosis in 114 cases (114/808, 14%). Cases without adenomyosis were found to have deeper myometrial invasion (P b .001) and those patients had a lower body mass index (P = .018). Median follow-up was 57 months (range, 0–183 months). Median overall survival for the entire cohort was not reached. Five-year overall survival for those with and without adenomyosis was 94% and 90%, respectively (P = .008). After controlling for stage and grade, however, the presence of adenomyosis was not associated with improved survival (HR 1.1, 95% CI 0.8–1.5). Within the adenomyosis group, there was no difference in overall survival (P = .54), disease-specific survival (P = .61), or recurrencefree survival (P = .84) when carcinoma involved adenomyosis. Conclusions: After controlling for other known prognostic factors, the presence of adenomyosis is not associated with survival in patients with endometrioid adenocarcinoma of the uterus. Adenocarcinoma involving adenomyosis does not alter the prognosis in patients with endometrial adenocarcinoma.
UN
CO
RR
EC
TE
DP
Objectives: Lynch syndrome (LS) confers hereditary predisposition to multiple tumors. The incidence of endometrial cancer (EC) can match colorectal carcinoma, with a risk of up to 60%. The frequency of germline mutations of mismatch repair protein (MMR-P) in unselected patients with EC is 1.8% to 2.1%. Our objective was to analyze the expression of MMR-P (MLH1, MSH2, MSH6, and PMS2) with immunohistochemistry (IHC) in tumor tissue of unselected patients with EC at our institution, and describe morphologic features associated with altered expression of MMR-P. Methods: We enrolled 84 patients with EC who were treated at the Hospital Italiano at Buenos Aires, Argentina, between April 2014 and August 2015. IHC for MLH1, MSH2, MSH6, and PMS2 was performed using the Ventana Benchmark XT system. The following variables were analyzed: expression of MMR-P, age, Lynch-associated morphologic characteristics, and tumor stage at diagnosis. Results: The mean age of our population was 64.7 years (standard deviation 12.45), 12 patients (14.5%) were younger than 50 years. Twenty-eight patients had altered expression of at least 1 MMR-P (33.3%). Twenty-one patients (75%) had a deficit of MLH1/PMS2, 2 of PMS2 (7%), 1 of MSH2/MSH6 (4%), and 4 of MSH6 (14%). Among the patients with altered IHC, only 2 were younger than 50 years. Regarding histologic subtypes, there were 24 (86%) endometrioid carcinomas, 1 clear cell carcinoma, 1 serous carcinoma, and 2 undifferentiated carcinomas. The mean body mass index was 31. We performed a complete morphologic study of 26 surgical specimens. In 17 cases (65%), we found at least 1 characteristic associated with altered expression of MMR-P (TM-MMR-P). One patient in the subset that did not show TMMMR-P features and one other met clinical criteria for LS. Of the 28 patients with altered expression, 25 were surgically treated at our hospital. FIGO stage distribution was as follows: 56% stage IA, 24% stage IB, and 20% stage III. Conclusions: The deficit of expression of MMR-P is consistent with that reported in the literature. Preliminary results in our population might support the routine use of IHC in selected patients with EC. Further comparative studies are needed to define elements of suspicion for LS in these patients.
RO
372 – Poster Endometrial cancer and Lynch syndrome: Immunohistochemical characterization of endometrial cancer associated with changes in mismatch repair protein expression M.C. Riggi, A. Wernicke, G. Salvo, G.T. Saraniti, J.P. Santino, M.C. Saez, C.A. Vaccaro, M. Perrotta. Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
OF
TOV112D-Scr (IC50:6.5 μM), SKOV3-ip-Scr (IC50: 8 μM), and A2780CP70-Scr (IC50: 88 μM). Conclusions: MYB is overexpressed in OC and demonstrates altered growth, malignant behavior, and chemoresistance of OC. These data provide the first experimental evidence for a functional role of the novel MYB oncogene in OC.
doi:10.1016/j.ygyno.2016.04.404
373 – Poster Locally advanced cervical squamous cell carcinoma (CSCC): Impact of the FDG PET/CT in the primary staging Withdrawn at author’s request doi:10.1016/j.ygyno.2016.04.405
doi:10.1016/j.ygyno.2016.04.406
375 – Poster Trends in robotic surgery for endometrial cancer and the impact of hospital surgical volume on perioperative complications M.S. Guya, J. Sheederb, E.L. Eisenhauera, T.J. Reidc, S.R. Guntupallib. a University of Cincinnati, UC Health Medical Arts Building, Cincinnati, OH, USA, bUniversity of Colorado Denver, Aurora, CO, USA, cUniversity of Cincinnati, Cincinnati, OH, USA Objectives: We examine 5-year trends in robotic surgery for endometrial cancer and evaluate the impact of hospital robotic volume on surgical outcomes. Methods: Using the Healthcare Cost and Utilization Project National (Nationwide) Inpatient Sample (HCUP-NIS) Database from 2008 to 2012, patients who underwent robotic surgery for endometrial cancer were identified. Surgical (intraoperative and perioperative) complications were abstracted. Medical comorbidity scores were calculated using the Charlson comorbidity index (CCI). High-volume
Abstracts / Gynecologic Oncology 141 (2016) 2–208
achieved in ARK1 cells genetically by silencing AXL with shRNA (P = .0131) or therapeutically by selective inhibition of AXL with R428 in combination with paclitaxel (P = .0036). The novel delivery system, p5RHH, conjugated to siAXL, was shown to inactivate AXL in ARK1 cells at the RNA and protein level to a similar extent as traditional transfection technique (8.4-fold vs 8.7-fold decrease for RNA, respectively; 67% vs 83% knockdown at 48 hours and 84% vs 97% knockdown at 96 hours for protein, respectively). Conclusions: AXL expression is associated with chemoresistance in ovarian and uterine cell lines. Genetic inactivation of AXL or targeted therapy using R428 in taxane-resistant uterine cells reverses chemoresistance. To find a targeted therapy to mimic this genetic inactivation, both a novel AXL kinase inhibitor and a novel siRNA nano-particle delivery system were successfully used.
OF
doi:10.1016/j.ygyno.2016.04.408
377 – Poster Preparing for a paradigm shift in the treatment of ovarian cancer: Effect of online CME on oncologists' knowledge and competence T. Herrmanna, S. Pearcea, M. Millera, D.S. Dizonb. aMedscape Education, New York, NY, USA, bMassachusetts General Hospital/Harvard University, Boston, MA, USA Objectives: We sought to determine the effect of online continuing medical education on the knowledge and competence of oncologists regarding the use of poly ADP ribose polymerase (PARP) inhibitors in ovarian cancer. Methods: The effect of 2 educational interventions on the role of PARP inhibition in the treatment of ovarian cancer was analyzed to determine efficacy of online education. The activities launched online in August 2014 and April 2015, and data were collected through November 2014 and May 2015, respectively. The effects of education were assessed by comparing the same group of participants’ responses to knowledge- and case-based matched pre- postassessments. A paired 2-tailed t test was used to assess whether the mean postassessment score was different from the mean preassessment score. The McNemar χ2 statistic was used to measure changes in responses to individual questions. The effect size was calculated with the Cohen d. Results: A total of 151 oncologist responses during the study period were included in this outcomes analysis. Significant improvements in the knowledge of the rationale for targeting PARP inhibition and its link to synthetic lethality were seen as a result of participation in video lecture (n = 62, large effect d = 1.287, P b .05) and case-based roundtable (n = 91, large effect d = 1.352, P b .05). After participation, 44% were more likely to recognize that all patients with ovarian cancer should be tested for BRCA mutations (P b .05), 27% were more likely to correctly counsel appropriate patients on the potential efficacy of PARP inhibitors in the management of their disease (P b .05), and 33% were more likely to identify the correlation among BRCA mutations, PARP inhibitors, and overall survival as reported in the literature. In a patient with ovarian cancer whose disease was BRCA wild-type, more oncologists were able to identify the potential clinical efficacy of combining a PARP inhibitor with vascular endothelial growth factor blockade in this patient population (P b .05). Conclusions: This study demonstrates the effectiveness of online education that uses multiple formats and reinforces prior learning on improving knowledge and competence of oncologists regarding the use of PARP inhibitors in the management of ovarian cancer. Additional studies are needed to assess whether improved knowledge and competence translate to clinical practice.
TE
DP
centers were defined as hospitals that completed more cases than the median for each year in the dataset. We compared patient characteristics, procedures, and outcomes, and examined trends over the 5-year period. A multivariable analysis (MVA) was completed to identify independent predictors of surgical complications in the robotic cohort. Results: A total of 7,066 patients were identified. Over the study period, rates of obesity increased (P b .001) as well as the CCI (P = .001). Lymph node dissection was less commonly performed (P b .001). Surgery volume increased in small or medium-sized (P b .001), private (P b .001), and teaching (P b0.001) hospitals. High-volume centers were more likely to be large (74% vs 62%, P b .001), teaching hospitals (78% vs 58%, P b .001), located in the northeastern or western United States, and were less likely to be privately owned (22% vs 31%, P b .001). Patients treated at highvolume centers were similar in age (P = .11), but had higher CCI values (2.5 ± 0.9 vs 2.6 ± 1.2, P = .002) and were more likely to undergo lymph node dissection (73% vs 68%, P = .007). MVA models included age, race, CCI, obesity, lymph node dissection, hospital size, ownership, teaching status, location, and volume. Increasing age (adjusted odds ratio [aOR] 1.02; 95% CI 1.02–1.03), CCI (aOR 1.25, 95% CI 1.18–1.33), obesity (aOR 1.50, 95% CI 1.30–1.73), and teaching hospital (aOR 1.23, 95% CI 1.05–1.45) independently predicted having a surgical complication. Large (aOR 0.85, 95% CI 0.74–0.99) or high-volume (aOR 0.81, 95% CI 0.66–0.98) hospital and Caucasian race (aOR 0.84, 95% CI 0.71–0.99) were associated with lower risk of complication. With increasing year of the procedure, patients were less likely to have a surgical complication (aOR 0.86, 95% CI 0.81–0.91). Conclusions: The strongest independent predictor of improved intraoperative and perioperative outcomes in robotic surgery for endometrial cancer is having surgery at a high-volume center.
RO
156
doi:10.1016/j.ygyno.2016.04.407
RR
EC
376 – Poster AXL, a receptor tyrosine kinase, mediates platinum and taxane resistance in ovarian and uterine cancer M. Palisoul, M. Nguyen, H. Pan, A. Lohrey, R. Desai, S. Wickline, M.A. Powell, D.G. Mutch, K.C. Fuh. Washington University School of Medicine in St. Louis, St. Louis, MO, USA
UN
CO
Objectives: Expression of AXL is associated with a worse prognosis in ovarian cancer. We investigated the role of AXL expression in chemotherapy response in ovarian and uterine cancers, and sought to reverse chemoresistance through inactivation of AXL. Methods: In vitro cell viability (XTT) assays were performed to confirm response to chemotherapy in SKOV3-S/R (platinum sensitive/ resistant ovarian cell lines), OVCAR3/TP (taxane sensitive/resistant ovarian cell lines), and AN3CA/ARK1 (taxane sensitive/resistant uterine cell lines), and Western blotting was performed for AXL expression. XTT assays of ARK1 cells for paclitaxel resistance with AXL silencing by shRNA were performed. This was then repeated with selective small molecule inhibition of AXL with R428. AXL knockdown by siRNA was performed with either a traditional transfection reagent (DharmaFECT) or with a novel serum-stable, cell-penetrating, endosomolytic amphipathic peptide delivery system (p5RHH). Cell viability assays were analyzed using paired t tests. P b .05 was considered statistically significant. Results: Chemoresistance was validated with XTT assays for SKOV3S/R, OVCAR3/TP, AN3CA/ARK1 (P = .0666, P = .0005, P b .0001, respectively). Western blotting confirmed overexpression of AXL in chemoresistant cell lines, and lack of AXL expression in their chemosensitive counterparts. Reversal of paclitaxel resistance was
doi:10.1016/j.ygyno.2016.04.409