- Email: [email protected]
Survivors of uterine malignancy have greater healthcare needs than the general population
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Abstracts / Gynecologic Oncology 137 (2015) 92–179
activity against breast cancer with HER2 amplifications. While up to 44% of uterine serous carcinoma (USC) harbor HER2 amplifications, Gynecologic Oncology Group 181B revealed that in patients with advanced/recurrent HER2-positive disease, trastuzumab produced minimal response. Our study sought to understand the effect of trastuzumab in HER2-amplified USC cell lines with or without PIK3CA mutations. Methods: In total, 17 USC cell lines were evaluated for PIK3 mutations by whole exome sequencing and HER2 amplification using fluorescence in situ hybridization. Based on having HER2 gene amplification with or without PIK3 “hot spot” (exon 9 and 20) mutations, four cell lines were chosen for experiments with trastuzumab. Six-day proliferation/ viability assays were carried out with scalar (from 0.01 μg/mL to 100 μg/mL) concentrations of trastuzumab to quantify cell viability vs. 100% viable controls. Results: A total of 41% of cell lines harbored HER2 amplification and 41% harbored PIK3 mutations. Of HER2-amplified, 57.1% harbored PIK3 mutations. In contrast, 20% without HER2 amplification were found to harbor PIK3 mutations. When the four cell lines with HER2 gene amplification were treated with trastuzumab, USC harboring oncogenic PIK3 mutations were highly resistant to trastuzumab compared with wild-type PIK3 cell lines (P = 0.02). A median inhibition concentration was not attained in PIK3-mutated cell lines. Conclusions: In USC, increased PIK3/AKT/mTOR pathway signaling and overexpression of HER2 are associated with aggressive disease and poor prognosis. For the first time, we demonstrated that USC with HER2 gene amplification commonly harbor oncogenic PIK3CA “hot spot” mutations in exons 9 and 20. More importantly, USC with simultaneous HER2 amplifications and PIK3CA mutations are resistant to trastuzumab and, thus, more dependent on the mTOR pathway to confer increased growth and survival advantage. While assessment of PIK3 pathway activation may provide a biomarker to identify patients unlikely to respond to singleagent trastuzumab-based therapy, the greater dependency of HER2amplified, PIK3-mutant USC cell lines to the PIK3/AKT/mTOR pathway suggest that trastuzumab combined with PIK3/AKT/mTOR inhibitors may represent a novel strategy against this subset of chemotherapy-resistant USC. doi:10.1016/j.ygyno.2015.01.404
402 — Poster Session Green (IGC) fluorescence directed sentinel lymph node (SLN) biopsy in women with endometrial and cervical cancer A. Urha, K.M. Robisona, C. Rakera, M. Steinhoffa, P.A. DiSilvestroa, C.K. McCourtb, C. Mathewsa, A.R. Stuckeya, C.O. Granaia, R.G. Moorea. a Women and Infants Hospital, Brown University, Providence, RI, USA, b Washington University School of Medicine, St. Louis, MO, USA Objectives: Determining which endometrial and cervical cancer patients will benefit from nodal staging is controversial. Sentinel lymph node (SLN) biopsy can be useful as an adjunct to lymphadenectomy in highrisk patients, but more importantly is employed as an alternative method of nodal evaluation for patients with low-risk tumors. The objectives of this study were to evaluate the surgical learning curve and to examine the performance characteristics of SLN dissection. Methods: This was an institutional review board-approved observational study examining women who had an isolated indocyanine green (ICG) SLN dissection or an ICG SLN dissection with a complete lymph node dissection (CND). Women who underwent an ICG SLN dissection from June 1, 2013 to August 5, 2014 were analyzed. STATA9 statistical software was used to analyze the database. Results: A total of 100 patients (94 endometrial and 6 cervical cancers) were identified. The mean age was 63.4 years and 76% of the tumors were endometrioid, 18% were other endometrial tumors, and 6% were small cell
cancer of the cervix. SLN was identified in 79% (160/200) of nodal basins, with 66% bilateral detection. Detection of bilateral SLNs was influenced by a learning curve; in the first 10 cases, bilateral SLNs were detected in only 56.1% (32/57) of cases. If a surgeon had done N10 cases, however, bilateral SLNs were detected in 79.1% (34/43) (P = 0.01). Twenty-eight patients had both SLN and bilateral CND performed, with a total of 73 nodal basins analyzed. SLN biopsy achieved a sensitivity of 90.9% with a specificity of 100%. The SLNs were external iliac (46.1%), obturator (48.1%), common iliac (2.4%), and aortic (2.9%), while positive nodes were either external iliac (47.1%) or obturator (52.9%). SLNs were the only positive nodes in 63.6% (7/11) of the patients; both SLNs and non-SLNs were positive in 27.3% (3/11). Microscopic metastasis in the SLN was detected in 36.4% (4/ 11) of patients. In one patient, a negative SLN was identified and there was a positive non-SLN on the ipsilateral nodal basin, which is a false-negative SLN rate of 9.1% (1/11). Conclusions: The bilateral SLN detection rate significantly improved after the surgeons' first 10 cases. SLN evaluation accurately reflects the nodal basin status for metastatic disease and can identify micrometastasis that may not have been detected with standard nodal evaluation. doi:10.1016/j.ygyno.2015.01.405
403 — Poster Session Survivors of uterine malignancy have greater healthcare needs than the general population K.C. Kurnita, K.K. Wardb, L.M. Beana, M.T. McHalea, C.C. Saenza, S.C. Plaxea. aUCSD Rebecca and John Moores Cancer Center, La Jolla, CA, USA, b University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA Objective: The objective of this study is to compare the comorbidities of women with uterine malignancy (UM) to controls so as to aid in development of survivorship care plans and programs. Methods: This retrospective cohort study using the University HealthSystem Consortium database evaluated women older than the age of 17 years who had a hysterectomy for UM between October, 2010 and March, 2014. Women without UM undergoing hysterectomy during the same time period served as controls. Frequencies and odds ratios (OR) of 26 distinct comorbidities were calculated for women with UM as compared to those without UM. Mantel Haenszel-stratified OR was used to correct for different age distributions between the UM and control groups using UHC predetermined age groups. Significance was defined as P b 0.05. Results: A total of 23,563 patients in the dataset had UM, and 142,610 patients were controls. Prior to stratification by age group, OR b 1, P b 0.05 were found for six comorbidities and OR N 1, P b 0.05 were found for 18 others. Uncorrected OR of ≥2 were found for hypertension (HTN), diabetes (DM), obesity (OB), congestive heart failure (CHF), pulmonary circulatory diseases (PCD), peripheral vascular disease (PVD), and renal failure (RF) (Table). Higher OR for UM remained significant after stratification by age as follows: HTN (OR = 1.7), DM (OR = 2.1), OB (OR = 3.3), CHF (OR = 1.5), PCD (OR = 1.7), and RF (OR = 1.2). The lowest ORs were seen for acquired immune deficiency syndrome (OR = 0.17), chronic blood loss anemia (OR = 0.36), and drug abuse (OR = 0.38). Conclusions: UM survivorship programs should plan for two to three times the need for management of HTN, DM, OB, CHF, PCD, and RF compared to the health care needs of the general public and between 20% and 300% greater needs compared to a population with comparable age distribution. Optimizing healthcare for UM survivors is enhanced by a comprehensive survivorship care plan. Appreciation of how the resources required differ from those required for the general population should facilitate planning and executing suitable and effective programs. Our findings suggest that provider education and provision of resources pertinent to patients with metabolic syndrome will be important components of effective UM survivorship care.
Abstracts / Gynecologic Oncology 137 (2015) 92–179
Comorbidities
Crude OR(95% CI)
Adjusted OR(95% CI)
Frequency in UM patients
Diabetes Hypertension Congestive heart failure Obesity Pulmonary circulatory diseases Peripheral vascular disease Renal failure Lymphoma Valvular disease Hypothyroid Paralysis Liver disease Fluid/electrolyte disorders Other neurologic diseases Weight loss Rheumatoid arthritis/collagen disease Depression Chronic pulmonary disorders Bleeding peptic ulcer disease Psychoses Coagulopathy Alcohol abuse Deficiency anemias Drug abuse Chronic blood loss anemia AIDS
3.33 3.24 3.05 2.99 2.90 2.58 2.32 1.84 1.81 1.77 1.52 1.44 1.32 1.30 1.23 1.18
(3.22–3.45) (3.15–3.33) (2.80–3.32) (2.90–3.08) (2.61–3.21) (2.29–2.91) (2.15–2.50) (1.42–2.38) (1.67–1.96) (1.71–1.85) (1.26–1.84) (1.29–1.61) (1.22–1.43) (1.19–1.42) (1.08–1.39) (1.08–1.30)
2.14 1.70 1.48 3.26 1.69 1.09 1.18 0.96 0.98 1.12 1.20 1.12 0.90 1.06 0.65 0.87
(2.07–2.22) (1.65–1.76) (1.35–1.61) (3.15–3.37) (1.52–1.89) (0.96–1.24) (1.09–1.28) (0.74–1.26) (0.90–1.07) (1.08–1.17) (0.97–1.47) (0.99–1.25) (0.83–0.98) (0.97–1.16) (0.57–0.73) (0.79–0.96)
25.9% 59.0% 3.5% 34.4% 2.3% 1.7% 4.0% 0.3% 3.4% 15.9% 0.6% 1.7% 3.2% 2.8% 1.3% 2.3%
1.16 1.12 1.06 0.95 0.79 0.77 0.63 0.38 0.36 0.17
(1.11–1.21) (1.07–1.17) (0.23–4.82) (0.86–1.04) (0.69–0.90) (0.65–0.91) (0.60–0.66) (0.32–0.46) (0.33–0.40) (0.07–0.37)
1.11 1.03 0.51 1.17 0.74 0.75 0.89 0.67 0.80 0.30
(1.06–1.16) (0.99–1.08) (0.11–2.48) (1.06–1.29) (0.65–0.86) (0.63–0.90) (0.84–0.93) (0.55–0.81) (0.72–0.88) (0.14–0.65)
11.3% 12.5% 0.01% 2.2% 1.1% 0.6% 9.0% 0.5% 2.0% 0.03%
doi:10.1016/j.ygyno.2015.01.406
404 — Poster Session Adjuvant vaginal brachytherapy decreases the risk of vaginal recurrence in patients with stage I non-invasive uterine papillary serous carcinoma H. Mahdi1, P.G. Rose1, M. Elshaikh2, A.R. Munkarah2, D. Isrow2, S. Singh3, S.E. Waggoner3, R. Ali-Fehmi4, J. Harding5, R.T. Morris4, R. DeBernardo1. 1Cleveland Clinic, Cleveland OH, USA, 2Henry Ford Health System, Detroit, MI, USA, 3University Hospitals – Case Medical Center, Cleveland, OH, USA, 4Wayne State University School of Medicine, Detroit, MI, USA, 5Case Western Reserve University, Cleveland, OH, USA Objectives: To investigate the impact of adjuvant vaginal brachytherapy on the risk of vaginal recurrence in stage I noninvasive uterine papillary serous carcinoma (UPSC). Methods: This retrospective study involved four United States academic centers from 2000 to 2012. Only patients with noninvasive (limited to the endometrium) stage IA UPSC were included. All patients underwent surgical treatment with at least total hysterectomy. The Kaplan–Meier method and Cox proportional hazards regression modeling were used. Results: Among 103 patients whose median age was 66 years (range, 49-90 years), 85% (88/103) underwent staging lymphadenectomy and 55% (59/103) had omentectomy. Postoperatively, 41.7% (43/ 103) were observed, 20% (21/103) received chemotherapy, and 38% (39/103) received vaginal brachytherapy +/- chemotherapy. A total of 28.2% (29/103) patients developed recurrence. The rate of vaginal, pelvic, and extrapelvic recurrences were 7.8% (8/103), 3.9% (4/103), and 16.5% (17/103), respectively. Among patients who were observed or received only chemotherapy, the rate of vaginal recurrence was 10.9% (7/64) compared to 2.6% (1/39) among those who received vaginal brachytherapy +/- chemotherapy (P=0.035). The rate of vaginal recurrence was not significantly different between those who were observed compared to those who received only chemotherapy (9.3% vs. 14.3%, P=0.27). The 5-year
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progression-free survival (PFS) and overall survival (OS) for the entire cohort were 88.3% and 90.6%, respectively. Patients who underwent lymphadenectomy had longer PFS (P=0.001) and OS (P=0.0005) compared to those who did not have lymphadenectomy. In multivariable analysis controlling for age, chemotherapy, brachytherapy, and lymphadenectomy, only lymphadenectomy was an independent predictor of PFS (HR 0.28, 95% CI 0.11-0.71, P=0.0037) and OS (HR 0.27, 95% CI 0.10-0.71, P=0.0035). Neither chemotherapy nor brachytherapy were a predictor of PFS or OS. Conclusions: In this largest study reported in stage I noninvasive UPSC, the majority of recurrence were extrapelvic. Vaginal brachytherapy has a significant role in reducing the risk of vaginal recurrence, and surgical staging was the only predictor of outcome. Therefore, both should be considered in stage I noninvasive UPSC. doi:10.1016/j.ygyno.2015.01.407
405 — Poster Session Trends and outcomes with utilization of plastic surgery for vulvar closure following vulvectomy for invasive squamous cell cancer E.M. Aviki, K.M. Esselen, S.M. Barcia, N.S. Horowitz, C.M. Feltmate, R.S. Berkowitz, M.R. Nucci, M.G. Muto. Brigham and Women's Hospital/Harvard University, Boston, MA, USA Objective: The objective of this study was to determine trends in utilization of plastic surgery consultation for vulvar closure following vulvectomy for invasive squamous cell cancer (iSCC). Methods: This retrospective cohort study involved women who underwent vulvectomy for iSCC from January 1, 2004 through October 31, 2013 at Brigham and Women's Hospital (BWH). Patients with iSCC present on pathology specimens were included. Slides were reviewed and margins determined by two pathologists. Clinical data were collected and statistically analyzed using XLSTAT-Pro v2014.2.02. Results: A total of 88 vulvectomies with iSCC on final pathology were identified during the study period. Fifteen (17%) had plastic surgery involved and 73 (83%) did not. Median age was 69 years (range, 32– 92 years). There was no difference in FIGO stage between groups, with a majority in both groups having stage I disease (80% and 70%, respectively). In the plastic surgery group, there were significantly more patients with diabetes mellitus (47% vs. 16%, P = 0.01), hypertension (87% vs. 52%, P = 0.013), recurrent disease (60% vs. 11%, P b 0.001), history of vulvectomy (27% vs. 11%, P = 0.001), and history of radiation therapy (33% vs. 5%, P = 0.001). Tumors were significantly larger in the plastic surgery group (3.73 cm vs. 2.03 cm, P b 0.001), yet there was no significant difference in achieving negative surgical margins (93% vs. 92%, P = 0.84). For tumors of ≥3.0 cm, plastic surgery was significantly associated with achieving adequate margins of ≥8 mm (50% vs. 7%, P = 0.039). The overall rate of postoperative complications was 41% and the rate was higher for cases involving plastic surgery (67% vs. 36%, P = 0.04). On univariate analysis, plastic surgery involvement (28% vs. 10%, P = 0.036), average tumor diameter (2.65 cm vs. 2.04 cm, P = 0.078), and preoperative radiation (89% vs. 11%, P = 0.003) were associated with complications. On multivariate analysis, only preoperative radiation was an independent, significant predictor of postoperative complications (OR 10.26, 95% CI 1.1–90.9). Conclusions: A review of BWH utilization confirms that the most complex patients with the largest lesions comprise the majority of cases that involve plastic surgery. Negative margins are equivalent and adequate margins in tumors of ≥3 cm are significantly improved by plastic surgery involvement, but a plastic surgery-assisted closure does not appear to affect postoperative complications. doi:10.1016/j.ygyno.2015.01.408
Abstracts / Gynecologic Oncology 137 (2015) 92–179
activity against breast cancer with HER2 amplifications. While up to 44% of uterine serous carcinoma (USC) harbor HER2 amplifications, Gynecologic Oncology Group 181B revealed that in patients with advanced/recurrent HER2-positive disease, trastuzumab produced minimal response. Our study sought to understand the effect of trastuzumab in HER2-amplified USC cell lines with or without PIK3CA mutations. Methods: In total, 17 USC cell lines were evaluated for PIK3 mutations by whole exome sequencing and HER2 amplification using fluorescence in situ hybridization. Based on having HER2 gene amplification with or without PIK3 “hot spot” (exon 9 and 20) mutations, four cell lines were chosen for experiments with trastuzumab. Six-day proliferation/ viability assays were carried out with scalar (from 0.01 μg/mL to 100 μg/mL) concentrations of trastuzumab to quantify cell viability vs. 100% viable controls. Results: A total of 41% of cell lines harbored HER2 amplification and 41% harbored PIK3 mutations. Of HER2-amplified, 57.1% harbored PIK3 mutations. In contrast, 20% without HER2 amplification were found to harbor PIK3 mutations. When the four cell lines with HER2 gene amplification were treated with trastuzumab, USC harboring oncogenic PIK3 mutations were highly resistant to trastuzumab compared with wild-type PIK3 cell lines (P = 0.02). A median inhibition concentration was not attained in PIK3-mutated cell lines. Conclusions: In USC, increased PIK3/AKT/mTOR pathway signaling and overexpression of HER2 are associated with aggressive disease and poor prognosis. For the first time, we demonstrated that USC with HER2 gene amplification commonly harbor oncogenic PIK3CA “hot spot” mutations in exons 9 and 20. More importantly, USC with simultaneous HER2 amplifications and PIK3CA mutations are resistant to trastuzumab and, thus, more dependent on the mTOR pathway to confer increased growth and survival advantage. While assessment of PIK3 pathway activation may provide a biomarker to identify patients unlikely to respond to singleagent trastuzumab-based therapy, the greater dependency of HER2amplified, PIK3-mutant USC cell lines to the PIK3/AKT/mTOR pathway suggest that trastuzumab combined with PIK3/AKT/mTOR inhibitors may represent a novel strategy against this subset of chemotherapy-resistant USC. doi:10.1016/j.ygyno.2015.01.404
402 — Poster Session Green (IGC) fluorescence directed sentinel lymph node (SLN) biopsy in women with endometrial and cervical cancer A. Urha, K.M. Robisona, C. Rakera, M. Steinhoffa, P.A. DiSilvestroa, C.K. McCourtb, C. Mathewsa, A.R. Stuckeya, C.O. Granaia, R.G. Moorea. a Women and Infants Hospital, Brown University, Providence, RI, USA, b Washington University School of Medicine, St. Louis, MO, USA Objectives: Determining which endometrial and cervical cancer patients will benefit from nodal staging is controversial. Sentinel lymph node (SLN) biopsy can be useful as an adjunct to lymphadenectomy in highrisk patients, but more importantly is employed as an alternative method of nodal evaluation for patients with low-risk tumors. The objectives of this study were to evaluate the surgical learning curve and to examine the performance characteristics of SLN dissection. Methods: This was an institutional review board-approved observational study examining women who had an isolated indocyanine green (ICG) SLN dissection or an ICG SLN dissection with a complete lymph node dissection (CND). Women who underwent an ICG SLN dissection from June 1, 2013 to August 5, 2014 were analyzed. STATA9 statistical software was used to analyze the database. Results: A total of 100 patients (94 endometrial and 6 cervical cancers) were identified. The mean age was 63.4 years and 76% of the tumors were endometrioid, 18% were other endometrial tumors, and 6% were small cell
cancer of the cervix. SLN was identified in 79% (160/200) of nodal basins, with 66% bilateral detection. Detection of bilateral SLNs was influenced by a learning curve; in the first 10 cases, bilateral SLNs were detected in only 56.1% (32/57) of cases. If a surgeon had done N10 cases, however, bilateral SLNs were detected in 79.1% (34/43) (P = 0.01). Twenty-eight patients had both SLN and bilateral CND performed, with a total of 73 nodal basins analyzed. SLN biopsy achieved a sensitivity of 90.9% with a specificity of 100%. The SLNs were external iliac (46.1%), obturator (48.1%), common iliac (2.4%), and aortic (2.9%), while positive nodes were either external iliac (47.1%) or obturator (52.9%). SLNs were the only positive nodes in 63.6% (7/11) of the patients; both SLNs and non-SLNs were positive in 27.3% (3/11). Microscopic metastasis in the SLN was detected in 36.4% (4/ 11) of patients. In one patient, a negative SLN was identified and there was a positive non-SLN on the ipsilateral nodal basin, which is a false-negative SLN rate of 9.1% (1/11). Conclusions: The bilateral SLN detection rate significantly improved after the surgeons' first 10 cases. SLN evaluation accurately reflects the nodal basin status for metastatic disease and can identify micrometastasis that may not have been detected with standard nodal evaluation. doi:10.1016/j.ygyno.2015.01.405
403 — Poster Session Survivors of uterine malignancy have greater healthcare needs than the general population K.C. Kurnita, K.K. Wardb, L.M. Beana, M.T. McHalea, C.C. Saenza, S.C. Plaxea. aUCSD Rebecca and John Moores Cancer Center, La Jolla, CA, USA, b University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA Objective: The objective of this study is to compare the comorbidities of women with uterine malignancy (UM) to controls so as to aid in development of survivorship care plans and programs. Methods: This retrospective cohort study using the University HealthSystem Consortium database evaluated women older than the age of 17 years who had a hysterectomy for UM between October, 2010 and March, 2014. Women without UM undergoing hysterectomy during the same time period served as controls. Frequencies and odds ratios (OR) of 26 distinct comorbidities were calculated for women with UM as compared to those without UM. Mantel Haenszel-stratified OR was used to correct for different age distributions between the UM and control groups using UHC predetermined age groups. Significance was defined as P b 0.05. Results: A total of 23,563 patients in the dataset had UM, and 142,610 patients were controls. Prior to stratification by age group, OR b 1, P b 0.05 were found for six comorbidities and OR N 1, P b 0.05 were found for 18 others. Uncorrected OR of ≥2 were found for hypertension (HTN), diabetes (DM), obesity (OB), congestive heart failure (CHF), pulmonary circulatory diseases (PCD), peripheral vascular disease (PVD), and renal failure (RF) (Table). Higher OR for UM remained significant after stratification by age as follows: HTN (OR = 1.7), DM (OR = 2.1), OB (OR = 3.3), CHF (OR = 1.5), PCD (OR = 1.7), and RF (OR = 1.2). The lowest ORs were seen for acquired immune deficiency syndrome (OR = 0.17), chronic blood loss anemia (OR = 0.36), and drug abuse (OR = 0.38). Conclusions: UM survivorship programs should plan for two to three times the need for management of HTN, DM, OB, CHF, PCD, and RF compared to the health care needs of the general public and between 20% and 300% greater needs compared to a population with comparable age distribution. Optimizing healthcare for UM survivors is enhanced by a comprehensive survivorship care plan. Appreciation of how the resources required differ from those required for the general population should facilitate planning and executing suitable and effective programs. Our findings suggest that provider education and provision of resources pertinent to patients with metabolic syndrome will be important components of effective UM survivorship care.
Abstracts / Gynecologic Oncology 137 (2015) 92–179
Comorbidities
Crude OR(95% CI)
Adjusted OR(95% CI)
Frequency in UM patients
Diabetes Hypertension Congestive heart failure Obesity Pulmonary circulatory diseases Peripheral vascular disease Renal failure Lymphoma Valvular disease Hypothyroid Paralysis Liver disease Fluid/electrolyte disorders Other neurologic diseases Weight loss Rheumatoid arthritis/collagen disease Depression Chronic pulmonary disorders Bleeding peptic ulcer disease Psychoses Coagulopathy Alcohol abuse Deficiency anemias Drug abuse Chronic blood loss anemia AIDS
3.33 3.24 3.05 2.99 2.90 2.58 2.32 1.84 1.81 1.77 1.52 1.44 1.32 1.30 1.23 1.18
(3.22–3.45) (3.15–3.33) (2.80–3.32) (2.90–3.08) (2.61–3.21) (2.29–2.91) (2.15–2.50) (1.42–2.38) (1.67–1.96) (1.71–1.85) (1.26–1.84) (1.29–1.61) (1.22–1.43) (1.19–1.42) (1.08–1.39) (1.08–1.30)
2.14 1.70 1.48 3.26 1.69 1.09 1.18 0.96 0.98 1.12 1.20 1.12 0.90 1.06 0.65 0.87
(2.07–2.22) (1.65–1.76) (1.35–1.61) (3.15–3.37) (1.52–1.89) (0.96–1.24) (1.09–1.28) (0.74–1.26) (0.90–1.07) (1.08–1.17) (0.97–1.47) (0.99–1.25) (0.83–0.98) (0.97–1.16) (0.57–0.73) (0.79–0.96)
25.9% 59.0% 3.5% 34.4% 2.3% 1.7% 4.0% 0.3% 3.4% 15.9% 0.6% 1.7% 3.2% 2.8% 1.3% 2.3%
1.16 1.12 1.06 0.95 0.79 0.77 0.63 0.38 0.36 0.17
(1.11–1.21) (1.07–1.17) (0.23–4.82) (0.86–1.04) (0.69–0.90) (0.65–0.91) (0.60–0.66) (0.32–0.46) (0.33–0.40) (0.07–0.37)
1.11 1.03 0.51 1.17 0.74 0.75 0.89 0.67 0.80 0.30
(1.06–1.16) (0.99–1.08) (0.11–2.48) (1.06–1.29) (0.65–0.86) (0.63–0.90) (0.84–0.93) (0.55–0.81) (0.72–0.88) (0.14–0.65)
11.3% 12.5% 0.01% 2.2% 1.1% 0.6% 9.0% 0.5% 2.0% 0.03%
doi:10.1016/j.ygyno.2015.01.406
404 — Poster Session Adjuvant vaginal brachytherapy decreases the risk of vaginal recurrence in patients with stage I non-invasive uterine papillary serous carcinoma H. Mahdi1, P.G. Rose1, M. Elshaikh2, A.R. Munkarah2, D. Isrow2, S. Singh3, S.E. Waggoner3, R. Ali-Fehmi4, J. Harding5, R.T. Morris4, R. DeBernardo1. 1Cleveland Clinic, Cleveland OH, USA, 2Henry Ford Health System, Detroit, MI, USA, 3University Hospitals – Case Medical Center, Cleveland, OH, USA, 4Wayne State University School of Medicine, Detroit, MI, USA, 5Case Western Reserve University, Cleveland, OH, USA Objectives: To investigate the impact of adjuvant vaginal brachytherapy on the risk of vaginal recurrence in stage I noninvasive uterine papillary serous carcinoma (UPSC). Methods: This retrospective study involved four United States academic centers from 2000 to 2012. Only patients with noninvasive (limited to the endometrium) stage IA UPSC were included. All patients underwent surgical treatment with at least total hysterectomy. The Kaplan–Meier method and Cox proportional hazards regression modeling were used. Results: Among 103 patients whose median age was 66 years (range, 49-90 years), 85% (88/103) underwent staging lymphadenectomy and 55% (59/103) had omentectomy. Postoperatively, 41.7% (43/ 103) were observed, 20% (21/103) received chemotherapy, and 38% (39/103) received vaginal brachytherapy +/- chemotherapy. A total of 28.2% (29/103) patients developed recurrence. The rate of vaginal, pelvic, and extrapelvic recurrences were 7.8% (8/103), 3.9% (4/103), and 16.5% (17/103), respectively. Among patients who were observed or received only chemotherapy, the rate of vaginal recurrence was 10.9% (7/64) compared to 2.6% (1/39) among those who received vaginal brachytherapy +/- chemotherapy (P=0.035). The rate of vaginal recurrence was not significantly different between those who were observed compared to those who received only chemotherapy (9.3% vs. 14.3%, P=0.27). The 5-year
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progression-free survival (PFS) and overall survival (OS) for the entire cohort were 88.3% and 90.6%, respectively. Patients who underwent lymphadenectomy had longer PFS (P=0.001) and OS (P=0.0005) compared to those who did not have lymphadenectomy. In multivariable analysis controlling for age, chemotherapy, brachytherapy, and lymphadenectomy, only lymphadenectomy was an independent predictor of PFS (HR 0.28, 95% CI 0.11-0.71, P=0.0037) and OS (HR 0.27, 95% CI 0.10-0.71, P=0.0035). Neither chemotherapy nor brachytherapy were a predictor of PFS or OS. Conclusions: In this largest study reported in stage I noninvasive UPSC, the majority of recurrence were extrapelvic. Vaginal brachytherapy has a significant role in reducing the risk of vaginal recurrence, and surgical staging was the only predictor of outcome. Therefore, both should be considered in stage I noninvasive UPSC. doi:10.1016/j.ygyno.2015.01.407
405 — Poster Session Trends and outcomes with utilization of plastic surgery for vulvar closure following vulvectomy for invasive squamous cell cancer E.M. Aviki, K.M. Esselen, S.M. Barcia, N.S. Horowitz, C.M. Feltmate, R.S. Berkowitz, M.R. Nucci, M.G. Muto. Brigham and Women's Hospital/Harvard University, Boston, MA, USA Objective: The objective of this study was to determine trends in utilization of plastic surgery consultation for vulvar closure following vulvectomy for invasive squamous cell cancer (iSCC). Methods: This retrospective cohort study involved women who underwent vulvectomy for iSCC from January 1, 2004 through October 31, 2013 at Brigham and Women's Hospital (BWH). Patients with iSCC present on pathology specimens were included. Slides were reviewed and margins determined by two pathologists. Clinical data were collected and statistically analyzed using XLSTAT-Pro v2014.2.02. Results: A total of 88 vulvectomies with iSCC on final pathology were identified during the study period. Fifteen (17%) had plastic surgery involved and 73 (83%) did not. Median age was 69 years (range, 32– 92 years). There was no difference in FIGO stage between groups, with a majority in both groups having stage I disease (80% and 70%, respectively). In the plastic surgery group, there were significantly more patients with diabetes mellitus (47% vs. 16%, P = 0.01), hypertension (87% vs. 52%, P = 0.013), recurrent disease (60% vs. 11%, P b 0.001), history of vulvectomy (27% vs. 11%, P = 0.001), and history of radiation therapy (33% vs. 5%, P = 0.001). Tumors were significantly larger in the plastic surgery group (3.73 cm vs. 2.03 cm, P b 0.001), yet there was no significant difference in achieving negative surgical margins (93% vs. 92%, P = 0.84). For tumors of ≥3.0 cm, plastic surgery was significantly associated with achieving adequate margins of ≥8 mm (50% vs. 7%, P = 0.039). The overall rate of postoperative complications was 41% and the rate was higher for cases involving plastic surgery (67% vs. 36%, P = 0.04). On univariate analysis, plastic surgery involvement (28% vs. 10%, P = 0.036), average tumor diameter (2.65 cm vs. 2.04 cm, P = 0.078), and preoperative radiation (89% vs. 11%, P = 0.003) were associated with complications. On multivariate analysis, only preoperative radiation was an independent, significant predictor of postoperative complications (OR 10.26, 95% CI 1.1–90.9). Conclusions: A review of BWH utilization confirms that the most complex patients with the largest lesions comprise the majority of cases that involve plastic surgery. Negative margins are equivalent and adequate margins in tumors of ≥3 cm are significantly improved by plastic surgery involvement, but a plastic surgery-assisted closure does not appear to affect postoperative complications. doi:10.1016/j.ygyno.2015.01.408