Genetic Differences Between BRCA-Associated and Sporadic Ovarian Cancer DNA

Overall, PFS was 54.3 months and OS was 57.0 months. Inpatients with pelvic nodal counts ≤15, PFS was 57.9 monthsvs. 50.6 months when N15 nodes were removed (p=0.169). OSwas 59.8 months (≤15 nodes) vs. 54.1 months (N15 nodes)(p=0.270). 29 (14%) patients had lymph node metastases. PFSwas 34.7 months in patients with positive lymph nodes vs. 57.4in patients without nodal metastases (p=0.001). OS was 40.5months in patients with lymph node metastasis and 59.6 in thosewithout (p=0.002). A total of 30 patients recurred; 14 (13%)had 15 or fewer nodes removed and 16 (16%) had N15 nodesremoved (p=0.45). No difference in survival was demonstratedbetween nodal groups in the 32 (15%) patients with poorlydifferentiated histology (PFS 55.5 months [≤15 nodes] vs.47.05 months [N15 nodes], p=0.24); OS 58.25 months [≤15nodes] vs. 51.85 months [N15 nodes], p=0.283).

Conclusion. The extent of lymph node dissection does notseem to have an effect on the outcome of patients diagnosedwith early stage adenocarcinoma of the cervix treated withradical hysterectomy and lymphadenectomy.

doi:10.1016/j.ygyno.2007.08.025

16Analysis of Intermediate Risk Factor Endometrial Cancer:Does Lymphadenectomy Affect Survival?G.S. Leiserowitz, G.B. Xing, A. Parikh-Patel, R. Cress,A. Abidi, A.O. Rodriguez, J.L. DalrympleUC Davis Medical Center, Sacramento, CA, California CancerRegistry, Sacramento, CA

Objectives. Intermediate risk factor endometrial cancer(defined as Stage IC, grades 1 and 2; or Stage IA–IC, grade3) patients are at increased risk for regional nodal metastases.We analyzed California endometrial cancer (EC) patients toassess lymphadenectomy rates, use of radiation therapy, andsurvival factors.

Methods. The California Cancer Registry database wasqueried for EC cases reported from 1994 to 2001. Using AJCCstaging criteria, we identified two groups of EC pts: Low risk(EC-LR: Stage IA, IB; grades 1 and 2) and intermediate risk(EC-IR, defined above) based on the “T” stage. Clinical dataincluding demographics, lymphadenectomy rates, nodal status,and use of radiation therapy were extracted. Statistical analysesincluded t-test, Chi-square, Cox proportional hazard ratios, andKaplan–Meier survival analysis.

Results. In this study, 14,933 EC patients had low riskdisease and 6518 had a intermediate risk disease. EC-IR wasmore frequent in African-American women than EC-LR (6.2 vs.2.8%, pb0.0001). The lymphadenectomy rates were higher inthe EC-IR group than the EC-LR group (56.8 vs. 35.7%,pb0.0001). The rate of metastatic nodes was higher in the EC-IR group than the EC-LR group (17.6% vs. 1.5%, pb0.0001).Involvement by a Gyn Oncologist was more common in the EC-IR group than the EC-LR group (26.4 vs. 17.9%, pb0.0001).Gyn Oncologists performed lymph node assessments more

frequently than other specialists in EC-IR pts (67.2 vs. 53.5%,pb0.0001). Radiation therapy was prescribed more frequentlyin EC-IR pts if lymphadenectomy was performed than when notperformed (49.6 vs. 38.4%, pb0.0001).

Lymphadenectomy had marginal effect on survival in EC-LR patients (p=0.03), but did improve survival in EC-IRpatients (pb0.0001). Using Cox proportional hazard model-ing, both lymphadenectomy and radiation therapy wereassociated with improved survival for EC-IR pts [HR: 0.62(95% CI – 0.55, 0.69) and 0.74 (CI – 0.69, 0.80), res-pectively]. Survival was adversely affected when the nodalstatus was unknown in EC-IR pts, but did not affect survivalin EC-LR pts [HR: 1.97 (CI – 1.79, 2.17) vs. 1.06 (0.93,1.21)]. Lymphadenectomy had less benefit for EC-LR pts[HR: 0.85 (CI – 0.74, 0.98)], and radiation was associatedwith adverse survival [HR: 1.35 (CI – 1.21, 1.50)].

Conclusions. Lymphadenectomy is very important in mana-ging EC-IR patients. Radiation therapy appears to be usedappropriately in EC-IR patients, but does not eliminate theadverse survival risks associated with deep myometrial invasionand high grade disease. Gyn Oncologists perform nodalassessment more frequently than other specialists in EC-IR pts.

doi:10.1016/j.ygyno.2007.08.026

17Genetic Differences Between BRCA-Associated andSporadic Ovarian Cancer DNAC.S. Walsh, S. Ogawa, D. Scoles, J. Pavelka, C. Miller,N. Kawamata, S. Narod, H.P. Koeffler, B.Y. KarlanCedars-Sinai Medical Center, Los Angeles, CAUniversity of Tokyo, Tokyo, JapanUniversity of Toronto, Toronto, Canada

Objectives. To compare the genetic alterations occurring inBRCA-associated versus sporadic epithelial ovarian cancer.

Methods. DNA was isolated from fresh, frozen, ovariancancer tissue obtained at the time of primary cytoreductivesurgery from 20 patients with papillary serous ovarian cancer. Awhole-genome copy number analysis of ovarian cancer DNAwas performed using the Affymetrix 50K Xba Mapping Array,using each patient's normal genomic DNA as the matchedcontrol. Genomic abnormalities were classified as amplifica-tions, deletions, or uniparental disomy (UPD, defined as loss ofone allele and duplication of the remaining allele), with orwithout loss of heterozygosity (LOH). Germline DNA wastested for BRCA mutations for all 20 patients. BRCA1 exon 11and BRCA2 exons 10 and 11 were screened by proteintruncation testing. Three Ashkenazi founder mutations andBRCA1 exon13 ins6kb mutation were tested by gel electro-phoresis. Genomic abnormalities were compared betweenBRCA positive and negative groups.

Results. All patients had papillary serous ovarian cancertreated with surgical cytoreduction and platinum basedchemotherapy. Among the 20 patients, median age was 62

367ABSTRACTS / Gynecologic Oncology 107 (2007) 360–381

(range 45–72), 18 (90%) were Caucasian, 9 (45%) were Jewish,2 had stage IIC, 14 had stage III, and 4 had stage IV disease.Median progression-free survival was 14 months (range 0.1–39.2) and overall survival was 42.9 months (range 11.5–90.5).Six patients (30%) carried BRCA germline mutations (fourBRCA1, one BRCA2, one BRCA1 and BRCA2). Among the20 cases, the percent of genome altered varied from 4 to 100%,with a median of 67.4%. Patients with germline BRCAmutations had tumors with greater alterations (median 89.6%,range 54–100%) compared to BRCA negative patients (median49.8%, range 4–85.6%), p=0.009. We used frequencyhistograms to demonstrate the proportion of cases affected byeach type abnormality at each genomic region. BRCA-associated tumors were more likely to have amplifications andloss of heterozygosity (LOH). This increase in LOH wasprimarily due to an increased occurrence of UPD in BRCA-associated tumors. Deletions were found more commonly innon-BRCA ovarian cancers.

Conclusions. Substantial differences occur in the frequencyand types of genetic abnormalities in BRCA-associated versussporadic ovarian cancer. BRCA-associated tumors are char-acterized by increased genomic instability, frequent amplifica-tions, frequent LOH due to UPD, and less frequent deletions.

doi:10.1016/j.ygyno.2007.08.027

18Stage IVb Endometrial Cancer: Does Applying an OvarianCancer Treatment Paradigm Result in Similar Outcomes?L.M. Landrum, K.N. Moore, T.K.N. Myers, G.S. Lanneau,J.L. Walker, M.A. GoldSection of Gynecologic Oncology, Department of Obstetricsand Gynecology, University of Oklahoma Health SciencesCenter, Oklahoma City, OK

Objective. The pattern of metastasis for stage IVendometrialcarcinoma (EC) is similar to that for ovarian carcinoma (OC),hence the goal of initial surgical management for both diseaseprocesses is optimal cytoreduction (CRS) followed by adjuvantchemotherapy. The objective of this study is to evaluate overallsurvival (OS) and progression-free survival (PFS) in patients(pts) with advanced EC compared to a cohort of pts with OCmatched for age and residual disease.

Methods. Pts with stage IVB EC treated with curative intentbetween the years 1990–2006 were identified. Pts not under-going primary surgical management, those with non-epithelialtumors, and those with disease outside the abdominal cavitywere excluded. Charts were abstracted for data regardingdemographics, surgical procedures, pathologic factors, andfollow-up. Two pts with stage IIIC OC were matched for eachstage IVB EC pt based on age and residual disease. All OC ptsunderwent primary CRS and received combination platinumbased chemotherapy to follow. PFS and OS were evaluatedusing Kaplan–Meier curves and log-rank analyses. Significancewas defined as pb0.05.

Results. Fifty-five patients with stage IVB EC underwentprimary surgical management and adjuvant therapy with cura-tive intent. The median age was 63 years (range 33–87) and84% were Caucasian. Optimal CRS (b1 cm residual disease)was achieved in 87% of patients (n=48). The most commonhistologic subtypes were serous (53%, n=29), endometrioid(44%, n=24), and clear cell (3%, n=2). Adjuvant therapy withcurative intent included platinum based combination che-motherapy (60%, n=33), platinum based chemotherapy withradiation (25%, n=14) and radiation alone (15%, n=8)depending on the time period in which the patient as treated.With a median follow-up of 24 months, 2-year OS for the entirecohort was 52 vs. 76% for pts with EC as compared to OC(p=0.05). Seven pts had residual disease N1 cm following CRS,6 of whom received chemotherapy alone. two-year OS forsuboptimal EC pts was 33% vs. 63% for OC pts (p=ns).Controlling for residual disease, EC pts with optimal CRS hadOS of 57% at 2 years compared to 82% for OC pts (p=0.03).PFS was strikingly similar between optimal EC and OC pts with2-year PFS of 44 vs. 45%, respectively (p=ns).

Conclusions. The treatment paradigm for advanced EC hasundergone a drastic evolution from palliation to CRS andcombination chemotherapy. Despite outward similarities indisease distribution and even histology, overall outcome for ptswith stage IVb EC does not approach that of pts with OC. Ourdata would suggest that this may be driven by poorer responseto salvage therapies among EC pts. Primary therapy appears togenerate similar outcomes for both EC and OC pts asdemonstrated by the similar PFS values for each disease entity.This may be due to a lack of active salvage agents or due to amore chemoresistant tumor as compared to OC pts. Furtherresearch to identify active salvage regimens for recurrent EC ptsmay improve outcome among Stage IVb EC pts.

doi:10.1016/j.ygyno.2007.08.028

19Catheter-Related Complications of IntraperitonealChemotherapy as First-Line Treatment for AdvancedEpithelial Ovarian CarcinomaL.M. Landrum, M.A. Gold, D.S. Mcmeekin, J.L. WalkerSection of Gyn Oncology, University of Oklahoma HealthSciences Center; Oklahoma City, OK

Objective. Intraperitoneal (IP) chemotherapy has a clearsurvival advantage in patients with advanced ovarian cancer,but a high rate of complications has discouraged widespreadacceptance. The purpose of this study was to review thecompletion rate of patients receiving IP chemotherapy as firstline treatment at a single institution and determine what factorsprohibit completion of therapy.

Methods. Patients receiving IP chemotherapy from 1993 to2006 were identified by hospital registries for a retrospectivereview. Charts were abstracted for patient demographics,clinical and pathologic findings, surgical intervention, treatmentmodalities, and toxicity.

368 ABSTRACTS / Gynecologic Oncology 107 (2007) 360–381