2
Results: We identied 198 patients who underwent SSCR for their rst recurrence. The median age was 56 years (range, 2780 years). Breakdown by initial stage of disease was: I (31), II (29), III (132), IV (6). There were 128 serous, 44 endometrioid, 12 clear cell, 6 mucinous, 5 carcinosarcoma, and 3 other histological types. Residual disease after SSCR was: 0 (114), b 5 mm (26), b 10 mm (14), N 1 cm (44). Recurrence occurred in 162 patients after SSCR during a median follow-up of 45.4 months (range, 1.2234.7 months). A nomogram was constructed using four signicant variables. Internal validation was performed using bootstrapping, and the model was shown to have a 95% CI of 0.667. Conclusions: We identied four prognostic factors for PFS after SSCR for recurrent EOC: number of recurrence sites, residual disease after SSCR, disease-free interval, and BRCA status. Using these four pre- dictor variables, we developed a nomogram to predict an individual patient's 5-year PFP. With external validation, this tool may be helpful in patient counseling, postoperative management, and deter- mining clinical trial eligibility. doi:10.1016/j.ygyno.2014.03.267 248 - Poster Session A Lymphadenectomy in stage I ovarian granulosa cell tumors improves overall survival S.E. Taylor 1 , M. Courtney-Brooks 2 , M. Quimper 1 , J.T. Comerci 1 , A.B. Olawaiye 1 , J.L. Kelley 2 , M. Huang 1 , P. Sukumvanich 1 . 1 Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA, 2 University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Objectives: Granulosa cell tumors are staged according to Interna- tional Federation of Gynecology and Obstetrics ovarian cancer staging guidelines with stage being the most important prognostic factor. Previous small, retrospective reviews have suggested that lymph node dissection can be eliminated from the staging process for early stage disease given the rarity of metastatic disease to the lymph nodes. The objective of this study is to determine the effect of lymphadenectomy on overall survival in patients with stage I ovarian granulosa cell tumors. Methods: Patients with granulosa cell tumors of the ovary were identied from the National Cancer Data Base between 1998 and 2011. Patients with clinical stage T1/N0/M0 and pathologic stage T1/ NX or NO/M0 disease were divided into those who underwent a lymph node assessment and those who did not. Demographic data, clinical and pathologic details, adjuvant treatment, and vital status were extracted. Student's t-test, Chi-square or Fisher's exact test was used for all univariate analysis. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Results: Out of 3060 patients with ovarian granulosa cell tumors identied, only 46 (1.5%) had documented lymph node involvement. There were 1693 patients with stage I disease and 1609 who had data recorded regarding the performance of lymph node dissection. Of evaluable stage I patients, 975 (57.6%) had lymph node assessment and 634 (37.4%) did not. These groups were no different with regards to age, race, Charlson/Deyo comorbidity score, tumor grade, LVSI, type and frequency of adjuvant therapy. Patients who underwent lymphadenectomy had a larger mean tumor size (11.2 vs 9.5 cm, p b 0.001). The 5-yr and 10-yr overall survival (OS) for those with stage I disease who had lymphadenectomy was 98.8% and 95.7% compared to 94.4% and 87.5%, respectively for those who had no lymph node assessment, translating into a mean OS of 157.4 vs 140.2 months (p b 0.001)(Fig. 1). Conclusions: Metastatic lymph node involvement is rare in ovarian granulosa cell tumors. However, even among patients with stage I disease, lymphadenectomy appears to confer an overall survival advantage indicating that abandonment of routine lymphadenecto- my based on retrospective studies may be premature. doi:10.1016/j.ygyno.2014.03.268 249 - Poster Session A Risk of second primary breast cancer among women with epithelial ovarian cancer compared to fallopian tube cancer J.A. Rauh-Hain 1 , J.T. Clemmer 1 , R.M. Clark 1 , T.R. Hall 2 , W.B. Growdon 2 , D.M. Boruta 1 , A. Goodman 1 , J.O. Schorge 1 , M.G. Del Carmen 1 . 1 Massachusetts General Hospital/Harvard University, Boston, MA, USA, 2 Massachusetts General Hospital, Boston, MA, USA. Objectives: Women with a history of epithelial ovarian cancer (EOC) have a signicantly increased risk of developing a second primary breast cancer and vice versa. The risk in women with fallopian tube cancer (FTC) is unknown. The aim of this study was to compare the risk of second primary breast cancer after rst primary EOC and FTC. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program data for all 18 registries from 1988 through 2010 was reviewed to identify women with EOC and FTC. To minimize misclassication of metastases or undetected synchronous cancers, women with EOC and FTC who developed second primary breast cancers 4 months after the diagnosis of EOC or FTC were identied. Continuous variables were evaluated by Student's t test or WilcoxonMannWhitney test, as appropriate. Categorical variables were evaluated by chi-square test. Impact of tumor site on survival was analyzed using the KaplanMeier method. Factors predictive of outcome were compared using the Cox proportional hazards model. Results: Of 63,790 women included in this analysis, 61,565 (96.5%) women had EOC and 2225 (3.5%) had FTC. The mean age at diagnosis was 59 ± 15 years for women with EOC and 63 ± 12.0 years for FTC (P b 0.001). Patients with EOC had a higher rate of stage III (30% vs 18%, P b 0.001) and IV disease (24.5% vs 8%, P b 0.001). The time to diagnosis of secondary breast cancer was signicantly longer in women with EOC (64 months vs 44.4 months, P b 0.001). Women with EOC were less likely to develop breast cancer compared to those with FTC (1.2% vs 2.2%, P b 0.001), and the 5-year breast cancer diagnosis rate was lower in women with EOC (1.3% vs 2.7%, P = 0.001). After controlling for age at diagnosis of EOC or FTC, original stage, race, marital status, SEER registry, surgery, radiotherapy, grade, and histology, women with EOC were less likely to develop a secondary breast cancer (HR 0.64, 95 CI 0.470.89). In the whole population, women who developed a secondary breast cancer had an improved 5-year survival rate compared to women who did not develop breast cancer (83.5% vs 47.3%, P b 0.001). Abstracts / Gynecologic Oncology 133 (2014) 2207 101

Risk of second primary breast cancer among women with epithelial ovarian cancer compared to fallopian tube cancer

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Page 1: Risk of second primary breast cancer among women with epithelial ovarian cancer compared to fallopian tube cancer

Results: We identified 198 patients who underwent SSCR for their firstrecurrence. The median age was 56 years (range, 27–80 years).Breakdown by initial stage of disease was: I (31), II (29), III (132), IV(6). Therewere 128 serous, 44 endometrioid, 12 clear cell, 6mucinous, 5carcinosarcoma, and 3 other histological types. Residual disease afterSSCR was: 0 (114), b5 mm (26), b10 mm (14), N1 cm (44). Recurrenceoccurred in 162 patients after SSCR during a median follow-up of45.4 months (range, 1.2–234.7 months). A nomogram was constructedusing four significant variables. Internal validation was performed usingbootstrapping, and the model was shown to have a 95% CI of 0.667.Conclusions: We identified four prognostic factors for PFS after SSCRfor recurrent EOC: number of recurrence sites, residual disease afterSSCR, disease-free interval, and BRCA status. Using these four pre-dictor variables, we developed a nomogram to predict an individualpatient's 5-year PFP. With external validation, this tool may behelpful in patient counseling, postoperative management, and deter-mining clinical trial eligibility.

doi:10.1016/j.ygyno.2014.03.267

248 - Poster Session ALymphadenectomy in stage I ovarian granulosa cell tumorsimproves overall survivalS.E. Taylor1, M. Courtney-Brooks2, M. Quimper1, J.T. Comerci1, A.B.Olawaiye1, J.L. Kelley2, M. Huang1, P. Sukumvanich1. 1Magee-WomensHospital of UPMC, Pittsburgh, PA, USA, 2University of Pittsburgh MedicalCenter, Pittsburgh, PA, USA.

Objectives: Granulosa cell tumors are staged according to Interna-tional Federation of Gynecology and Obstetrics ovarian cancerstaging guidelines with stage being the most important prognosticfactor. Previous small, retrospective reviews have suggested thatlymph node dissection can be eliminated from the staging processfor early stage disease given the rarity of metastatic disease to thelymph nodes. The objective of this study is to determine the effect oflymphadenectomy on overall survival in patients with stage I ovariangranulosa cell tumors.Methods: Patients with granulosa cell tumors of the ovary wereidentified from the National Cancer Data Base between 1998 and2011. Patients with clinical stage T1/N0/M0 and pathologic stage T1/NX or NO/M0 disease were divided into those who underwent alymph node assessment and those who did not. Demographic data,clinical and pathologic details, adjuvant treatment, and vital statuswere extracted. Student's t-test, Chi-square or Fisher's exact test wasused for all univariate analysis. Overall survival (OS) was calculatedusing the Kaplan-Meier method and compared using the log-ranktest.Results: Out of 3060 patients with ovarian granulosa cell tumorsidentified, only 46 (1.5%) had documented lymph node involvement.There were 1693 patients with stage I disease and 1609 who haddata recorded regarding the performance of lymph node dissection.Of evaluable stage I patients, 975 (57.6%) had lymph nodeassessment and 634 (37.4%) did not. These groups were no differentwith regards to age, race, Charlson/Deyo comorbidity score, tumorgrade, LVSI, type and frequency of adjuvant therapy. Patients whounderwent lymphadenectomy had a larger mean tumor size (11.2 vs9.5 cm, p b 0.001). The 5-yr and 10-yr overall survival (OS) for thosewith stage I disease who had lymphadenectomy was 98.8% and 95.7%compared to 94.4% and 87.5%, respectively for those who had nolymph node assessment, translating into a mean OS of 157.4 vs140.2 months (p b 0.001)(Fig. 1).Conclusions: Metastatic lymph node involvement is rare in ovariangranulosa cell tumors. However, even among patients with stage Idisease, lymphadenectomy appears to confer an overall survival

advantage indicating that abandonment of routine lymphadenecto-my based on retrospective studies may be premature.

doi:10.1016/j.ygyno.2014.03.268

249 - Poster Session ARisk of second primary breast cancer among women withepithelial ovarian cancer compared to fallopian tube cancerJ.A. Rauh-Hain1, J.T. Clemmer1, R.M. Clark1, T.R. Hall2, W.B. Growdon2,D.M. Boruta1, A. Goodman1, J.O. Schorge1, M.G. Del Carmen1.1Massachusetts General Hospital/Harvard University, Boston, MA, USA,2Massachusetts General Hospital, Boston, MA, USA.

Objectives: Women with a history of epithelial ovarian cancer (EOC)have a significantly increased risk of developing a second primarybreast cancer and vice versa. The risk in women with fallopian tubecancer (FTC) is unknown. The aim of this study was to compare therisk of second primary breast cancer after first primary EOC and FTC.Methods: The Surveillance, Epidemiology, and End Results (SEER)Program data for all 18 registries from 1988 through 2010was reviewedto identify women with EOC and FTC. To minimize misclassification ofmetastases or undetected synchronous cancers, women with EOC andFTC who developed second primary breast cancers 4 months after thediagnosis of EOC or FTC were identified. Continuous variables wereevaluated by Student's t test or Wilcoxon–Mann–Whitney test, asappropriate. Categorical variables were evaluated by chi-square test.Impact of tumor site on survival was analyzed using the Kaplan–Meiermethod. Factors predictive of outcome were compared using the Coxproportional hazards model.Results: Of 63,790 women included in this analysis, 61,565 (96.5%)women had EOC and 2225 (3.5%) had FTC. The mean age at diagnosiswas 59 ± 15 years for women with EOC and 63 ± 12.0 years for FTC(P b 0.001). Patients with EOC had a higher rate of stage III (30% vs 18%,P b 0.001) and IV disease (24.5% vs 8%, P b 0.001). The time to diagnosisof secondary breast cancer was significantly longer in women with EOC(64 months vs 44.4 months, P b 0.001). Women with EOC were lesslikely to develop breast cancer compared to thosewith FTC (1.2% vs 2.2%,P b 0.001), and the 5-year breast cancer diagnosis rate was lower inwomen with EOC (1.3% vs 2.7%, P=0.001). After controlling for age atdiagnosis of EOC or FTC, original stage, race, marital status, SEER registry,surgery, radiotherapy, grade, and histology, women with EOC were lesslikely to develop a secondary breast cancer (HR 0.64, 95 CI 0.47–0.89). Inthe whole population, womenwho developed a secondary breast cancerhad an improved 5-year survival rate compared to women who did notdevelop breast cancer (83.5% vs 47.3%, P b 0.001).

Abstracts / Gynecologic Oncology 133 (2014) 2–207 101

Page 2: Risk of second primary breast cancer among women with epithelial ovarian cancer compared to fallopian tube cancer

Conclusions:Womenwith FTCweremore likely to develop a secondaryprimary breast cancer. Women who developed breast cancer afterdiagnosis of EOC or FTC had an improved survival compared to womenwho do not did not.

doi:10.1016/j.ygyno.2014.03.269

250 - Poster Session APredicting overall survival after secondary surgical cytoreductionfor platinum-sensitive recurrent ovarian cancer:A prognostic nomogramC.H. Kim1, L. Kou2, C. Yu2, E. Conroy3, C.L. Brown4, N.R. Abu-Rustum4, G.J.Gardner4, V. Makker4, M.W. Kattan2, D.S. Chi4. 1Thomas JeffersonUniversity Hospital, Philadelphia, PA, USA, 2The Cleveland Clinic, Cleveland,OH, USA, 3Albert Einstein Montefiore Medical Center, New York, NY, USA,4Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Objective: Patients with platinum-sensitive epithelial ovarian cancer(EOC) recurrence who undergo secondary surgical cytoreduction(SSCR) have heterogeneous outcomes. Our objective was to identifyprognostic factors for overall survival (OS) to develop a nomogramthat could predict OS for an individual patient undergoing SSCR.Methods: We identified all EOC patients who underwent SSCR fortheir first recurrence at our institution from January 1991 toNovember 2009. We excluded all patients who recurred b6 monthsfrom their last platinum therapy and those who had second-linechemotherapy before SSCR. OS was calculated based on the date ofdeath or follow-up. We analyzed 11 clinicopathologic variables. ACox proportional hazards model then stepdown was employed toconstruct a predictive nomogram for internal validation (95% CI).Bootstrapping was used to correct optimistic bias.Results: Among 198 eligible patients, the median age was 56 years(range, 27-80 years). Initial stage III–IV disease was identified in 138(70%) patients. Histologies included 128 serous, 12 clear cell, 44endometrioid, 6 mucinous, 5 carcinosarcoma, and 3 other. Residualtumor after primary cytoreduction was: 0 (78 patients), 5 mm (45),10 mm (40), and N10 mm (35). Residual disease after SSCR was: 0(114 patients), b5 mm (26), b10 mm (14), and N10 mm (44). With amedian follow-up of 40.6 months (range, 1.2–180.6 months), 125deaths were observed. The median time to death was 53.6 months.Five significant prognostic factors for OS were identified onmultivariable analysis: disease-free interval, CA-125 level, ASA score,number of recurrence sites, and residual disease after SSCR. Anomogram using these five variables was constructed with boots-trapping for internal validation and shown to have a 95% CI of 0.719(Figure).Conclusions: We identified five prognostic factors for OS at thetime of SSCR for recurrent platinum-sensitive EOC. Using these pre-dictor variables, we developed a nomogram to predict an individualpatient's OS after SSCR with a 95% CI of 0.719. With externalvalidation, this tool may be helpful in patient counseling, selectionfor SSCR, postoperative management, and determining clinical trialeligibility.

doi:10.1016/j.ygyno.2014.03.270

251 - Poster Session AAcquired platinum resistance among women with high-gradeserous epithelial ovarian cancerK.N. Slaughter1, C.C. Gunderson1, L. Perry1, E.D. Thomas2, R. Farrell1,J.K. Lauer1, K. Ding1, D.S. McMeekin1, K.N. Moore1. 1The University ofOklahoma, Oklahoma City, OK, USA, 2Stephenson Cancer Center, TheUniversity of Oklahoma, Oklahoma City, OK, USA.

Objectives: Following primary chemotherapy, patients are categorizedas either primary platinum-sensitive (PPS) or acquired platinum-resistant (APR). Eventually, PPS patients develop resistance to platinumtherapies and can be characterized as APR. We sought to examine thenatural history of APR as compared to primary platinum resistance(PPR).Methods: Medical records of patients with high-grade serous ovariancancer (HGS-OVCA) treated at a single institution from 2000 through2010 were reviewed. PPR was defined as not achieving completeresponse (CR) with primary platinum therapy or recurrence b6 monthsfrom the end of therapy. APR was defined as CR with primary platinumtherapy and subsequent therapy with a platinum agent resulting inprogressive disease (PD) or recurrence within 6 months. Demographics,therapeutic modalities, and survival outcomes were abstracted andanalyzed.Results: Of 348 patients identified with HGS-OVCA, just over half(n=178)were PPS,while 23.3% (n=81)were PPR and 20.4% (n=71)were APR. Patients with APR had a median age of 61 years (range, 31–87 years). Stage III diseasewas diagnosed in 75%of patients. Themajorityof APR patients underwent primary debulking (86%); 13% receivedneoadjuvant therapy. The median number of therapy regimens was 4(range, 2–11), with a median of 4 (range, 2–8) cytotoxics and 1 (range,0–6) biologic. After amedian follow-up of 4 years, patients with APR hada median primary progression-free survival (PFS) of 21.3 months and amedian overall survival (OS) of 61.4 months. When calculated from thedate of APR, OS was approximately 21 months compared to 15 monthsfor PPR pts. There was no difference inmedian OS for APR patients basedon prior number of platinum-containing regimens received (P=0.26).Mean length of time to develop APR was approximately 38 months,which was similar to that for patients who received maintenancetherapy in the upfront setting and those who did not (37.7 months vs37.5 months, P=0.98). Once APR, 10% of patients survived more than4 years. Participation in clinical trials (P=0.006) and longer primary PFS(P=0.009) were associated with prolonged OS for patients with APR,while younger age (P=0.04), clinical trial participation (P=0.02), andnumber of biologic agents (P=0.006) predicted longer OS for PPRpatients.Conclusions: Prognosis following development of APR, while not asdire as for PPR, is still poor. Referral of these patients to clinical trialsof biologic and targeted agents appears to be the best option for PPRand APR patients.

doi:10.1016/j.ygyno.2014.03.271

252 - Poster Session ADifferential expression of Rad51 and NAC1 proteins in primary,metastatic, and recurrent high-grade serous ovarian cancerH. Mahdi, P.G. Rose, B. Yang. The Cleveland Clinic, Cleveland, OH, USA.

Objectives: Rad51 interacts with BRCA1/2 genes and plays a central rolein the homologous recombination pathway essential for repair of DNAdouble-strand breaks. On the other hand, NAC1 is a transcriptionsrepressor that has been reported to be associated with early recurrenceand chemotherapy resistance. The objective of this studywas to evaluatethe expression of Rad51 and NAC1 proteins in primary, metastatic, andrecurrent high-grade serous ovarian cancer.Methods: A total of 248 cases of high-grade serous ovarian cancer,including 79 primary (PT), 86 metastatic (MT) (from lymph nodes,omentum, and liver), and 83 recurrent tumors (RT) following initialadjuvant chemotherapy and secondary tumor reductive surgerywere constructed into tissue microarray. Immunohistochemicalstaining (IHC) using antibody against Rad51 and NAC1 proteins wasperformed. Nuclear and/or cytoplasmic expression was evaluated forRad51 and NAC1 based on the intensity of staining (graded 0–3).

Abstracts / Gynecologic Oncology 133 (2014) 2–207102