Molecular profile of uterine papillary serous carcinoma compared to ovarian serous carcinoma: Is it the same disease at different site?

Abstracts / Gynecologic Oncology 137 (2015) 92–179

for Medical Oncology criteria for LR-IR and HR of recurrence, and outcomes before and after the new guidelines were evaluated. Results: We included 230 LR-IR patients (159 before and 71 after) with 54 HR patients (33 before and 21 after). Pelvic lymphadenectomy was performed before and after the new guidelines in 123/159 (77.4%) and 20/71 (28.6%) patients, respectively (P b 0.001) in LH-IR. After 2010, eight patients with LH-IR also underwent secondary paraaortic lymphadenectomy for lymphovascular space invasion (LVSI), based on definitive histology. Overall survival (OS) and relapse-free survival (RFS) were similar before and after the new guidelines. In LR-RI patients, LVSI was an independent factor for OS (HR = 7.2, 95% CI: 3.1–17, P b 0.001) and RFS (HR = 3.7, 95% CI: 1.6–8.5, P b 0.003). After 2010, optimally managed LR-IR patients had similar OS and a higher 2-year RFS compared to suboptimally managed patients (OS: 100% vs. 98.1% [87.1– 99.7], P = 0.6; RFS: 94.1% [82.7–98.1] vs. 77.1% [44.2–92.1], P = 0.07). Conclusions: Fewer pelvic lymphadenectomies in LR-IR patients did not affect morbidity, OS, or RFS, and staged surgery did not affect morbidity or survival. However, a trend toward increased risk of recurrence was observed in patients who were not optimally managed per the new guidelines. Therefore, we must gather additional data, with a longer follow-up, to confirm our results. doi:10.1016/j.ygyno.2015.01.381

379 — Poster Session Weight change after participation in a technology-based weight loss intervention for endometrial cancer survivors with obesity A.F. Haggertya, G. Raggiob, J. Spitzera, D.B. Sarwera, E.M. Koa, C. Chuc, K. Allisona. aUniversity of Pennsylvania, Philadelphia, PA, USA, b University of Pennsylvania Health System, Philadelphia, PA, USA, cFox Chase Cancer Center, Philadelphia, PA, USA Objectives: Weight loss is believed to play an important role in reducing morbidity and mortality of endometrial cancer survivors and should be a primary objective of survivorship care. In this study, we investigated the efficacy and sustainability of a technology-based weight loss intervention in obese endometrial cancer survivors. Methods: Twenty women age N 18 years with obesity (body mass index ≥ 30) and histologically confirmed endometrial hyperplasia/ type I endometrial cancer were randomized 1:1 to a 6-month lifestyle modification intervention for weight loss delivered via the telephone or text messaging. Following completion of the program, prospective data from clinical cancer surveillance visits were abstracted to determine long-term weight changes at 9, 12, and 18 months compared to enrollment (t = 0 months). Descriptive statistics were performed. Results: The majority of initial participants had early-stage (65%) endometrial cancer and had a median age of 60.5 years. The primary intervention outcome revealed median weight loss of 9.7 kg at t = 6 months (range, 1.1–22.9 kg) in the telemedicine group compared with 3.9 kg (range, 0.3–11.4 kg, P = 0.023) in the text group. Weight loss was maintained during observational follow-up. At t = 9 months, 75% of the cohort successfully maintained weight loss, with a median loss of 2.7 kg (interquartile range [IQR] 0.8–5.7 kg) compared to t = 0. At t = 12 months, 69% demonstrated a median loss of 2.5 kg (IQR 1.4–6.1 kg). At t = 18 months, 79% had maintained a weight loss of 5.7 kg (1.4–11.4 kg) compared to baseline. Overall, the telemedicine arm continued to be more successful in maintaining weight loss at t = 9 months (P = 0.015), although there was no difference between the telemedicine and text groups at 12 (P = 0.79) and 18 months (P = 0.9) of follow-up. Conclusions: While a technology-based weight loss intervention was initially more successful in a telemedicine platform, participants in both

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arms continued to be successful in maintaining weight loss at 12 and 18 months after enrollment. Further investigation is needed to identify measures to improve sustainability of an initially successful weight loss intervention, perhaps by continuation of the intervention, development of a modified support system, or adaptation of a combination of initial telemedicine support followed by a text messaging platform. doi:10.1016/j.ygyno.2015.01.382

380 — Poster Session Is indocyanine green (ICG) the best tracer for sentinel lymph node (SLN) mapping in early-stage cervical and endometrial cancer? M. Plantea, O. Touhamib, X.B. Trinhb, J. Grégoireb, A. Sebastianellib, M.C. Renaudb. aLaval University, L'Hotel-Dieu de Quebec, Quebec City, QC, Canada, bL'Hotel-Dieu de Quebec, Québec, QC, Canada Objectives: Indocyanine green (ICG) with near-infrared (NIR) fluorescence imaging is a new tracer modality that appears to have a better detection rate and safety profile than blue dye and is less cumbersome to use than Tc-99. We present our initial experience with ICG for SLN mapping in cervical and endometrial cancer. Methods: We reviewed all patients at our institution who underwent primary surgery for presumed early-stage endometrial and cervical carcinoma with SLN mapping using the ICG dye and fluorescence imaging followed by pelvic lymphadenectomy from February to July 2014. SLNs were ultrastaged on final pathology. Sensitivity and specificity values were calculated. Results: A total of 50 patients were included in the study (42 endometrial and 8 cervical cancers). The mean age was 59 years (range, 24–88 years). Mean body mass index was 31 (range, 19– 56). The mean SLN count was 3.1 (range, 0–7) and the median lymph node count was 16 (range, 2–37). The overall detection rate was 96% (48/50), with a bilateral detection rate of 88% (44/50). Positive SLNs were identified in 22% of patients (11/50), including eight isolated tumor cells (ITC), two micrometastases, and one macrometastasis. Sensitivity and specificity values were 100%. Paraaortic node dissection was performed in 22% of cases. Two had paraaortic node metastasis, both in patients with positive pelvic SLNs. There were no adverse effects or allergic reactions related to the ICG dye. Conclusions: Based on our pilot experience, NIR fluorescence imaging with ICG is an excellent and safe tracer modality for SLN mapping, with a very high overall (96%) and bilateral (88%) detection rate. We believe that ICG is ideal for large-scale worldwide implementation of SLN mapping in early-stage cervical and endometrial cancer. doi:10.1016/j.ygyno.2015.01.383

381 — Poster Session Molecular profile of uterine papillary serous carcinoma compared to ovarian serous carcinoma: Is it the same disease at different site? H. Mahdia, J. Xiub, S.K. Reddyb, R. DeBernardoa. aCleveland Clinic, Cleveland, OH, USA, bCaris Life Sciences, Irving, TX, USA Objectives: To compare the molecular profile of a large cohort of uterine papillary serous carcinoma (UPSC) and ovarian serous carcinoma (EOC-S). Methods: A total of 240 UPSC and 1587 EOC-S tumors were evaluated using a commercial multiplatform profiling service (CARIS Life Sciences, Phoenix, AZ). Specific testing performed included a combination of gene sequencing (Sanger, NGS), protein expression (immunohistochemistry [IHC]), and gene amplification

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Abstracts / Gynecologic Oncology 137 (2015) 92–179

(chromogenic in situ hybridization or fluorescence in situ hybridization). Results: TP53 was the most commonly mutated gene in both UPSC and EOC-S (76% vs. 69%, P = 0.03). UPSC tumors were more likely to have mutation in PIK3CA (29% vs. 2%, P b 0.001), FBXW7 (12% vs. 1%, P b 0.001), KRAS (9% vs. 5%, P b 0.001), PTEN (7% vs. 1%, P b 0.001), and CTNNB1 (2% vs. 0%, P b 0.001) compared to EOC-S. On the other hand, EOC-S tumors were more likely to harbor mutation in BRCA1 (20% vs. 9%) and BRCA2 (18% vs. 6%), although this difference was not statistically significant (P = 0.12 and P = 0.08, respectively). No difference in the rate of mutation of APC (3% vs. 3%), ATM (3% vs. 2%), BRAF (1% vs. 1%), and AKT1 (1% vs. 0.2%) was identified (P b 0.05 for all). IHC MRP-1 (88% vs. 83%, P = 0.07), PD-1 (68% vs. 68%, P = 0.9), PTEN (56% vs. 58%, P = 0.22), TOPO1 (36% vs. 40%, P = 0.06), and PR (32% vs. 30%, P = 0.39) were overexpressed in both USC and EOC-S. MGMT (80% vs. 53%, P b 0.001) was more expressed in EOC-S than UPSC. IHC TOP2A (89% vs. 69%, P b 0.001), ER (60% vs. 53%, P = 0.0008), RRM1 (35% vs. 27%, P b 0.001), HER2 ISH (17% vs. 4%, p b 0.001), and Her2/ neu (10% vs. 2%, P b 0.001) were more expressed in UPSC than EOCS, respectively. Conclusions: UPSC tumors have a distinct mutation profile indicating higher activity of the PI3K/PTEN/MTOR pathway but no difference in alteration of the homologous recombination pathway compared to EOC-S. Overexpression of TOPO2A and other markers needs to be correlated with outcome and response to chemotherapy. doi:10.1016/j.ygyno.2015.01.384

382 — Poster Session Under-utilization of minimally invasive surgery in the management of endometrial cancer: A Healthcare Cost and Utilization Project-National Inpatient Sample study (HCUP-NIS) A. Nickles Fadera, R. Matsunob, A.K. Sinnoc, E.J. Tanner IIIc, K.C. Longc, R.E. Bristowd, S.C. Dowdye. aJohns Hopkins Medical Institutions, Baltimore, MD, USA, bUniversity of California San Diego Medical Group, La Jolla, CA, USA, c Johns Hopkins Hospital, Baltimore, MD, USA, dUniversity of California, Irvine, Irvine, CA, USA, eMayo Clinic, Rochester, MN, USA Objectives: Recently, the Society of Gynecologic Oncology (SGO) and the American College of Surgeons’ Commission on Cancer (CoC) approved two endometrial cancer (EC) quality indicators, including utilization of minimally invasive surgery (MIS) for the primary treatment of all patients with stage I-III EC. Our aim was to define case mix-adjusted hospital level utilization of MIS for hysterectomy ±staging (HYST) in the treatment of early-stage EC. Methods: We analyzed the United States Healthcare Cost and Utilization Project/Nationwide Inpatient Sample database from 2010 to 2011. Patients with nonmetastatic EC who underwent a HYST were analyzed. Hierarchical logistic regression models were used to evaluate hospital and patient variables associated with MIS utilization. Hospitals were categorized into thirds (low: b10 cases; medium: 11–30 cases; high: N30 cases) based on EC volume. Actual vs. SGO/CoC guideline-recommended MIS utilization for EC was compared (i.e., hospitals performing MIS in 85% or more of the early-stage EC population). Results: A total of 20,188 EC cases were identified, 88.1% of which were nonmetastatic. Of those, 69.0% patients underwent a HYST. There was discordance between actual and SGO/CoC guidelinerecommended utilization of MIS HYST. Overall, only 42.5% of nonmetastatic EC patients underwent MIS HYST, with a rate of 26.3% at low-volume centers (P b 0.001). Twenty percent of EC patients were treated at lower-volume facilities. After

multivariable adjustment, MIS HYST was less likely to occur in patients with comorbidities (Elixhauser score, OR 0.85; 95% CI 0.83, 0.88), with Medicaid vs. private insurance (OR 0.64; 95% CI 0.52, 0.78), in black vs. white patients (OR 0.42; 95% CI 0.35, 0.50), and in hospitals with a low vs. high EC volume (OR 0.46; 95% CI 0.30, 0.71). MIS HYST was more likely to occur in west vs. northeast hospitals (OR 2.0; 95% CI 1.31, 3.05). Finally, abdominal HYST was associated with a significantly higher risk of 30-day perioperative complications (OR 2.2; 94% CI 1.9, 2.4), surgical site infection (OR 1.9; 95% CI 1.6, 2.1), and N1 week hospital stay (OR 6.4; 95% CI 5.0, 8.1). Conclusions: Hospital utilization of MIS for the treatment of earlystage EC varies significantly in the United States, representing a disparity in the quality of surgical care delivered nationwide. This study has implications for quality improvement, as hospitals may have an opportunity to reduce perioperative morbidity and costs by increasing MIS utilization. doi:10.1016/j.ygyno.2015.01.385

383 — Poster Session Distinct molecular landscapes between endometrioid and non-endometrioid uterine carcinoma N.L. Jonesa, J. Xiub, S.K. Reddyb, A.I. Tergasa, W.M. Burkea, J.D. Wrighta, J.Y. Houa. aNYP/Columbia University Medical Center, New York, NY, USA, b Caris Life Sciences, Irving, TX, USA Objectives: Endometrial carcinoma (EC) is traditionally divided into endometrioid (type I) and nonendometrioid (type II) subtypes, despite considerable heterogeneity within each phenotype. Our aim was to identify distinct molecular alterations between histologic subtypes that would aid in guiding treatment strategies. Methods: A total of 3133 ECs were submitted to Caris Life Sciences between March 2011 and July 2014 (1634 type I and 1226 type II, based on reported pathology). Multiplatform molecular analysis included gene sequencing (Sanger or next generation sequencing), immunohistochemistry (IHC) of protein expression, and/or gene amplification (fluorescence in situ hybridization/chromogenic in situ hybridization). Proportion analysis was performed using Prism v.6. Results: Table 1 depicts the histologic breakdown of EC cases and major pathway aberrations. Histologic subtype was significantly associated with estrogen receptor (ER)/androgen receptor (AR) and cMET expression and PI3K, KRAS, and ERBB2 mutation. Endometrioid histology had the highest ER/progesterone receptor (PR) expression (81% and 69%, respectively), PD1/PDL-1 expression (74.3%/30.7%), and PI3K mutation (35.6%). AR expression (27%) and Her2/neu overexpression/amplification (10.4%/ 17.3%) was the highest in uterine serous carcinoma (USC). Mucinous tumors harbored a high KRAS mutation rate (41%) and cMET overexpression (43%). Clear cell (CC) cancer also had notably high cMET overexpression (40%) as well as ERBB2 mutation (8.3%). TP53 was mutated most frequently in USC (76%), followed by carcinosarcoma (CS) (69%). CS also had the lowest expression of ER/PR (25% and 21%), high expression of PD1/PDL-1 (84% and 25%), and high frequency of FBXW7 mutation (12%). Squamous histology was significant for high expression of beta catenin gene CTNNB1 (44%), implicated in the Wnt pathway. Altered DNA repair pathway, as indicated by BRCA mutations, and low ERCC1 and MGMT expressions were most notable in in CC, suggesting benefit with platinum therapy. Conclusions: Despite molecular heterogeneity among histologic subtypes, distinct patterns of pathway aberration may be targeted with further research. Correlating molecular profiles with clinical outcomes can assist in developing rational guidelines for therapy in individuals with EC.