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Stage IVb Endometrial Cancer: Does Applying an Ovarian Cancer Treatment Paradigm Result in Similar Outcomes?
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ABSTRACTS / 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 (four BRCA1, one BRCA2, one BRCA1 and BRCA2). Among the 20 cases, the percent of genome altered varied from 4 to 100%, with a median of 67.4%. Patients with germline BRCA mutations had tumors with greater alterations (median 89.6%, range 54–100%) compared to BRCA negative patients (median 49.8%, range 4–85.6%), p = 0.009. We used frequency histograms to demonstrate the proportion of cases affected by each type abnormality at each genomic region. BRCAassociated tumors were more likely to have amplifications and loss of heterozygosity (LOH). This increase in LOH was primarily due to an increased occurrence of UPD in BRCAassociated tumors. Deletions were found more commonly in non-BRCA ovarian cancers. Conclusions. Substantial differences occur in the frequency and types of genetic abnormalities in BRCA-associated versus sporadic ovarian cancer. BRCA-associated tumors are characterized by increased genomic instability, frequent amplifications, frequent LOH due to UPD, and less frequent deletions. doi:10.1016/j.ygyno.2007.08.027
18 Stage IVb Endometrial Cancer: Does Applying an Ovarian Cancer Treatment Paradigm Result in Similar Outcomes? L.M. Landrum, K.N. Moore, T.K.N. Myers, G.S. Lanneau, J.L. Walker, M.A. Gold Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK Objective. The pattern of metastasis for stage IV endometrial carcinoma (EC) is similar to that for ovarian carcinoma (OC), hence the goal of initial surgical management for both disease processes is optimal cytoreduction (CRS) followed by adjuvant chemotherapy. The objective of this study is to evaluate overall survival (OS) and progression-free survival (PFS) in patients (pts) with advanced EC compared to a cohort of pts with OC matched for age and residual disease. Methods. Pts with stage IVB EC treated with curative intent between the years 1990–2006 were identified. Pts not undergoing primary surgical management, those with non-epithelial tumors, and those with disease outside the abdominal cavity were excluded. Charts were abstracted for data regarding demographics, surgical procedures, pathologic factors, and follow-up. Two pts with stage IIIC OC were matched for each stage IVB EC pt based on age and residual disease. All OC pts underwent primary CRS and received combination platinum based chemotherapy to follow. PFS and OS were evaluated using Kaplan–Meier curves and log-rank analyses. Significance was defined as p b 0.05.
Results. Fifty-five patients with stage IVB EC underwent primary surgical management and adjuvant therapy with curative intent. The median age was 63 years (range 33–87) and 84% were Caucasian. Optimal CRS (b 1 cm residual disease) was achieved in 87% of patients (n = 48). The most common histologic subtypes were serous (53%, n = 29), endometrioid (44%, n = 24), and clear cell (3%, n = 2). Adjuvant therapy with curative intent included platinum based combination chemotherapy (60%, n = 33), platinum based chemotherapy with radiation (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 entire cohort 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 for suboptimal EC pts was 33% vs. 63% for OC pts (p = ns). Controlling for residual disease, EC pts with optimal CRS had OS of 57% at 2 years compared to 82% for OC pts (p = 0.03). PFS was strikingly similar between optimal EC and OC pts with 2-year PFS of 44 vs. 45%, respectively (p = ns). Conclusions. The treatment paradigm for advanced EC has undergone a drastic evolution from palliation to CRS and combination chemotherapy. Despite outward similarities in disease distribution and even histology, overall outcome for pts with stage IVb EC does not approach that of pts with OC. Our data would suggest that this may be driven by poorer response to salvage therapies among EC pts. Primary therapy appears to generate similar outcomes for both EC and OC pts as demonstrated by the similar PFS values for each disease entity. This may be due to a lack of active salvage agents or due to a more chemoresistant tumor as compared to OC pts. Further research to identify active salvage regimens for recurrent EC pts may improve outcome among Stage IVb EC pts. doi:10.1016/j.ygyno.2007.08.028
19 Catheter-Related Complications of Intraperitoneal Chemotherapy as First-Line Treatment for Advanced Epithelial Ovarian Carcinoma L.M. Landrum, M.A. Gold, D.S. Mcmeekin, J.L. Walker Section of Gyn Oncology, University of Oklahoma Health Sciences Center; Oklahoma City, OK Objective. Intraperitoneal (IP) chemotherapy has a clear survival advantage in patients with advanced ovarian cancer, but a high rate of complications has discouraged widespread acceptance. The purpose of this study was to review the completion rate of patients receiving IP chemotherapy as first line treatment at a single institution and determine what factors prohibit completion of therapy. Methods. Patients receiving IP chemotherapy from 1993 to 2006 were identified by hospital registries for a retrospective review. Charts were abstracted for patient demographics, clinical and pathologic findings, surgical intervention, treatment modalities, and toxicity.
ABSTRACTS / 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 (four BRCA1, one BRCA2, one BRCA1 and BRCA2). Among the 20 cases, the percent of genome altered varied from 4 to 100%, with a median of 67.4%. Patients with germline BRCA mutations had tumors with greater alterations (median 89.6%, range 54–100%) compared to BRCA negative patients (median 49.8%, range 4–85.6%), p = 0.009. We used frequency histograms to demonstrate the proportion of cases affected by each type abnormality at each genomic region. BRCAassociated tumors were more likely to have amplifications and loss of heterozygosity (LOH). This increase in LOH was primarily due to an increased occurrence of UPD in BRCAassociated tumors. Deletions were found more commonly in non-BRCA ovarian cancers. Conclusions. Substantial differences occur in the frequency and types of genetic abnormalities in BRCA-associated versus sporadic ovarian cancer. BRCA-associated tumors are characterized by increased genomic instability, frequent amplifications, frequent LOH due to UPD, and less frequent deletions. doi:10.1016/j.ygyno.2007.08.027
18 Stage IVb Endometrial Cancer: Does Applying an Ovarian Cancer Treatment Paradigm Result in Similar Outcomes? L.M. Landrum, K.N. Moore, T.K.N. Myers, G.S. Lanneau, J.L. Walker, M.A. Gold Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK Objective. The pattern of metastasis for stage IV endometrial carcinoma (EC) is similar to that for ovarian carcinoma (OC), hence the goal of initial surgical management for both disease processes is optimal cytoreduction (CRS) followed by adjuvant chemotherapy. The objective of this study is to evaluate overall survival (OS) and progression-free survival (PFS) in patients (pts) with advanced EC compared to a cohort of pts with OC matched for age and residual disease. Methods. Pts with stage IVB EC treated with curative intent between the years 1990–2006 were identified. Pts not undergoing primary surgical management, those with non-epithelial tumors, and those with disease outside the abdominal cavity were excluded. Charts were abstracted for data regarding demographics, surgical procedures, pathologic factors, and follow-up. Two pts with stage IIIC OC were matched for each stage IVB EC pt based on age and residual disease. All OC pts underwent primary CRS and received combination platinum based chemotherapy to follow. PFS and OS were evaluated using Kaplan–Meier curves and log-rank analyses. Significance was defined as p b 0.05.
Results. Fifty-five patients with stage IVB EC underwent primary surgical management and adjuvant therapy with curative intent. The median age was 63 years (range 33–87) and 84% were Caucasian. Optimal CRS (b 1 cm residual disease) was achieved in 87% of patients (n = 48). The most common histologic subtypes were serous (53%, n = 29), endometrioid (44%, n = 24), and clear cell (3%, n = 2). Adjuvant therapy with curative intent included platinum based combination chemotherapy (60%, n = 33), platinum based chemotherapy with radiation (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 entire cohort 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 for suboptimal EC pts was 33% vs. 63% for OC pts (p = ns). Controlling for residual disease, EC pts with optimal CRS had OS of 57% at 2 years compared to 82% for OC pts (p = 0.03). PFS was strikingly similar between optimal EC and OC pts with 2-year PFS of 44 vs. 45%, respectively (p = ns). Conclusions. The treatment paradigm for advanced EC has undergone a drastic evolution from palliation to CRS and combination chemotherapy. Despite outward similarities in disease distribution and even histology, overall outcome for pts with stage IVb EC does not approach that of pts with OC. Our data would suggest that this may be driven by poorer response to salvage therapies among EC pts. Primary therapy appears to generate similar outcomes for both EC and OC pts as demonstrated by the similar PFS values for each disease entity. This may be due to a lack of active salvage agents or due to a more chemoresistant tumor as compared to OC pts. Further research to identify active salvage regimens for recurrent EC pts may improve outcome among Stage IVb EC pts. doi:10.1016/j.ygyno.2007.08.028
19 Catheter-Related Complications of Intraperitoneal Chemotherapy as First-Line Treatment for Advanced Epithelial Ovarian Carcinoma L.M. Landrum, M.A. Gold, D.S. Mcmeekin, J.L. Walker Section of Gyn Oncology, University of Oklahoma Health Sciences Center; Oklahoma City, OK Objective. Intraperitoneal (IP) chemotherapy has a clear survival advantage in patients with advanced ovarian cancer, but a high rate of complications has discouraged widespread acceptance. The purpose of this study was to review the completion rate of patients receiving IP chemotherapy as first line treatment at a single institution and determine what factors prohibit completion of therapy. Methods. Patients receiving IP chemotherapy from 1993 to 2006 were identified by hospital registries for a retrospective review. Charts were abstracted for patient demographics, clinical and pathologic findings, surgical intervention, treatment modalities, and toxicity.