- Email: [email protected]
Is intraperitoneal chemotherapy as effective within the elderly population for the treatment of epithelial ovarian cancer?
Abstracts / Gynecologic Oncology 141 (2016) 2–208
OF
doi:10.1016/j.ygyno.2016.04.304
273 – Poster The evolution of estrogen receptor signaling in the progression of endometriosis to endometriosis-associated ovarian cancer M.M. Boisena, C. Andersenb, M. Sikorab, T. Mac, G. Tsengc, A. Vladd, E. Elishaeva, U. Chandrane, R.P. Edwardsa, S. Oesterreicha. aMageeWomens Hospital of UPMC, Pittsburgh, PA, USA, bUniversity of Pittsburgh/Magee-Women's Hospital, Pittsburgh, PA, USA, cUniversity of Pittsburgh, Pittsburgh, PA, USA, dMagee-Womens Research Institute, Pittsburgh, PA, USA, eUniversity of Pittsburgh/Magee-Women's Hosiptal, Pittsburgh, PA, USA
DP
doi:10.1016/j.ygyno.2016.04.303
1.55–10.10, P = .004) and residual disease (HR 2.67, 95% CI 1.29– 5.52, P = .008) were significant factors. Conclusions: Older EOC patients completed fewer cycles of IP/ intravenous chemotherapy without any significant increase in toxicity, dose delays or dose modifications, and comparable survival to younger patients. The numeric increase in neuropathy higher than grade 2 is a point of concern, especially in a more vulnerable population. The population of older patients receiving IP chemotherapy in this study were on clinical trial and likely to be healthier than the general elderly population. IP chemotherapy appears well tolerated and effective among older patients and is likely underutilized outside clinical trials.
RO
was performed to test where proportions of positive results were different by subgroup (P ≤ .05). Results: The study cohort had a median age of 65 years, consisted of 84% (120/143) squamous (SCC) and 16% (23/143) adenocarcinoma (ADC) histologies, and 46% of patients had metastatic disease (stage IV). Targeted hot-spot sequencing identified variants in the following genes, in descending order of frequency: TP53 (34%), PIK3CA/BRCA2 (8% each), HRAS/FBXW7 (5%-6% each) and ERBB4/ GNAS (3% each). Mutations in AKT1, ATM, FGFR2, KRAS, NRAS, and BRAF also occurred (n = 1 each). Specific protein changes for targetable genes included clinically pathogenic mutations commonly found in other cancer types (e.g., PIK3CA: exon 9 [E545K]; RAS: G13D, Q61L; BRCA2: S1667X; BRAF: R443T; and FBXW7: E471fs). Additional drug targets are identifiable using IHC and ISH methodologies, including cMET (32% IHC, 2% ISH), PDL1 (16%), PTEN loss (45%), HER2 (6% IHC, 2% ISH), and hormone receptors (AR, 6%; ER, 11%; PR, 4%). Comparisons between SCC and ADC identified differential rates for AR, ER, HER2, and GNAS, with an increased presence in ADC (P b .05 for all). Conclusions: Molecularly guided precision medicine could provide alternative, targeted treatment options for vulvar cancer patients especially because of the easy accessibility for repetitive biopsy.
113
Objectives: To investigate estrogen receptor (ER) signaling as a potential mechanism of malignant transformation of endometriosis into endometriosis-associated ovarian cancer (EAOC). Methods: Tissue samples of normal endometrium (n = 23), and benign (n = 19), atypical (n = 11), and concurrent (n = 9) endometrioisis and endometriosis-associated cancers (n = 20) were collected. To evaluate ER signaling, a 236-gene signature of estrogenregulated genes (the “E2sig”) was developed. RNA was isolated from each tissue specimen and expression of the E2sig was measured on the NanoString nCounter platform. Analysis of variance (ANOVA) and unsupervised clustering were used to identify differentially regulated genes and distinct gene expression profiles across samples. These profiles were compared with gene expression datasets of estrogen regulation using Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA) against the Molecular Signatures Database was performed to assess whether the pattern of gene expression was consistent with ER activity. Results: ANOVA revealed 158 differentially expressed genes (q b 0.05) and unsupervised clustering of this subset identified 4 distinct gene clusters. Cluster 1 includes genes with increasing expression from benign endometriosis to EAOC and best represents genes involved in malignant transformation. The most notable genes in this cluster are FGF18 and ESR2 (ERβ). Clusters 2 and 3 include genes that are highly expressed and underexpressed in EAOC compared with endometriosis, respectively. Cluster 4 includes genes with an incremental decrease in expression from benign endometriosis to EAOC and includes ESR1 (ERα)) and several downstream ER targets (e.g., PGR, GREB1). Compared with datasets of classic ERα signaling profiles identified in GEO, profiles of EAOC differed significantly. Likewise, GSEA analysis did not identify any ER-related signatures activated in EAOC and among those ownregulated genes, GSEA identified signatures consistent with endocrine resistance and loss of ER function. (See Fig. 1.) Conclusions: Gene expression data suggest classic ER signaling decreases in the progression of endometriosis to EAOC. The gene expression pattern in EAOC is more consistent with profiles of endocrine resistance. FGF18 and ESR2 may play an important role in malignant transformation.
TE
272 – Poster Is intraperitoneal chemotherapy as effective within the elderly population for the treatment of epithelial ovarian cancer? A.K. Crima, M. Rowlanda, R. Ruskina, J. Dvorakb, M. Greenwadeb, A. Waltera, J. Gillenb, K. Dingc, K.N. Moorec, C.C. Gundersonc. aThe University of Oklahoma, Stephenson Cancer Center, Oklahoma City, OK, USA, bUniversity of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, cThe University of Oklahoma, Oklahoma City, OK, USA
UN
CO
RR
EC
Objectives: Intraperitoneal (IP) chemotherapy for the treatment of epithelial ovarian cancer (EOC) has been shown to provide a substantial advantage in overall survival, and is now considered the standard of care. As the US population ages, evaluating these treatments, specifically for patients with this condition, is of utmost importance. This study aims to compare the toxicity and benefits of IP chemotherapy in patients of ages 70 years and older with those younger than 70 years. Methods: We performed a single institution retrospective review of patients diagnosed with stage IIA-IIIC EOC from 2000 to 2013 who received IP chemotherapy. Clinicopathologic characteristics were extracted, and survival was calculated. SAS version 9.3 was used for descriptive statistics and multivariate analyses. Results: A total of 133 patients were included, with 100 patients being younger than 70 years and 33 patients aged 70 years or older. Race, stage, histology, and performance status were similar. Residual disease did not differ (P = .23). All patients received a platinum/ taxane doublet for frontline chemotherapy. Clinical trial enrollment was similar (89% vs 90%, P = 1.00) despite age. In trial-enrolled patients, older patients received statistically fewer cycles of therapy (6.4 vs 5.8, P = .002) but had similar dose delays (0.9 vs 0.3, P = .17) and dose modifications (1.00 vs 0.93, P = .91). Median progressionfree survival (27 vs 31 months) and overall survival (71 and 62 months) were not statistically different. Grade 4 heme toxicities (P = 1.0), and grade 3 and higher non-heme toxicities (6.1% vs 6.7%, P = 1.0) were similar between groups. Although not statistically significant, neuropathy grade higher than 2 trended higher in the older group (100 vs 86%; P = .18). Upon multivariate analysis for overall survival, age less than 70 years (HR 0.697, 95% CI 0.36–1.26, P = .23) was not predictive, but stage (IIIC vs lower: HR 3.95, 95% CI
OF
doi:10.1016/j.ygyno.2016.04.304
273 – Poster The evolution of estrogen receptor signaling in the progression of endometriosis to endometriosis-associated ovarian cancer M.M. Boisena, C. Andersenb, M. Sikorab, T. Mac, G. Tsengc, A. Vladd, E. Elishaeva, U. Chandrane, R.P. Edwardsa, S. Oesterreicha. aMageeWomens Hospital of UPMC, Pittsburgh, PA, USA, bUniversity of Pittsburgh/Magee-Women's Hospital, Pittsburgh, PA, USA, cUniversity of Pittsburgh, Pittsburgh, PA, USA, dMagee-Womens Research Institute, Pittsburgh, PA, USA, eUniversity of Pittsburgh/Magee-Women's Hosiptal, Pittsburgh, PA, USA
DP
doi:10.1016/j.ygyno.2016.04.303
1.55–10.10, P = .004) and residual disease (HR 2.67, 95% CI 1.29– 5.52, P = .008) were significant factors. Conclusions: Older EOC patients completed fewer cycles of IP/ intravenous chemotherapy without any significant increase in toxicity, dose delays or dose modifications, and comparable survival to younger patients. The numeric increase in neuropathy higher than grade 2 is a point of concern, especially in a more vulnerable population. The population of older patients receiving IP chemotherapy in this study were on clinical trial and likely to be healthier than the general elderly population. IP chemotherapy appears well tolerated and effective among older patients and is likely underutilized outside clinical trials.
RO
was performed to test where proportions of positive results were different by subgroup (P ≤ .05). Results: The study cohort had a median age of 65 years, consisted of 84% (120/143) squamous (SCC) and 16% (23/143) adenocarcinoma (ADC) histologies, and 46% of patients had metastatic disease (stage IV). Targeted hot-spot sequencing identified variants in the following genes, in descending order of frequency: TP53 (34%), PIK3CA/BRCA2 (8% each), HRAS/FBXW7 (5%-6% each) and ERBB4/ GNAS (3% each). Mutations in AKT1, ATM, FGFR2, KRAS, NRAS, and BRAF also occurred (n = 1 each). Specific protein changes for targetable genes included clinically pathogenic mutations commonly found in other cancer types (e.g., PIK3CA: exon 9 [E545K]; RAS: G13D, Q61L; BRCA2: S1667X; BRAF: R443T; and FBXW7: E471fs). Additional drug targets are identifiable using IHC and ISH methodologies, including cMET (32% IHC, 2% ISH), PDL1 (16%), PTEN loss (45%), HER2 (6% IHC, 2% ISH), and hormone receptors (AR, 6%; ER, 11%; PR, 4%). Comparisons between SCC and ADC identified differential rates for AR, ER, HER2, and GNAS, with an increased presence in ADC (P b .05 for all). Conclusions: Molecularly guided precision medicine could provide alternative, targeted treatment options for vulvar cancer patients especially because of the easy accessibility for repetitive biopsy.
113
Objectives: To investigate estrogen receptor (ER) signaling as a potential mechanism of malignant transformation of endometriosis into endometriosis-associated ovarian cancer (EAOC). Methods: Tissue samples of normal endometrium (n = 23), and benign (n = 19), atypical (n = 11), and concurrent (n = 9) endometrioisis and endometriosis-associated cancers (n = 20) were collected. To evaluate ER signaling, a 236-gene signature of estrogenregulated genes (the “E2sig”) was developed. RNA was isolated from each tissue specimen and expression of the E2sig was measured on the NanoString nCounter platform. Analysis of variance (ANOVA) and unsupervised clustering were used to identify differentially regulated genes and distinct gene expression profiles across samples. These profiles were compared with gene expression datasets of estrogen regulation using Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA) against the Molecular Signatures Database was performed to assess whether the pattern of gene expression was consistent with ER activity. Results: ANOVA revealed 158 differentially expressed genes (q b 0.05) and unsupervised clustering of this subset identified 4 distinct gene clusters. Cluster 1 includes genes with increasing expression from benign endometriosis to EAOC and best represents genes involved in malignant transformation. The most notable genes in this cluster are FGF18 and ESR2 (ERβ). Clusters 2 and 3 include genes that are highly expressed and underexpressed in EAOC compared with endometriosis, respectively. Cluster 4 includes genes with an incremental decrease in expression from benign endometriosis to EAOC and includes ESR1 (ERα)) and several downstream ER targets (e.g., PGR, GREB1). Compared with datasets of classic ERα signaling profiles identified in GEO, profiles of EAOC differed significantly. Likewise, GSEA analysis did not identify any ER-related signatures activated in EAOC and among those ownregulated genes, GSEA identified signatures consistent with endocrine resistance and loss of ER function. (See Fig. 1.) Conclusions: Gene expression data suggest classic ER signaling decreases in the progression of endometriosis to EAOC. The gene expression pattern in EAOC is more consistent with profiles of endocrine resistance. FGF18 and ESR2 may play an important role in malignant transformation.
TE
272 – Poster Is intraperitoneal chemotherapy as effective within the elderly population for the treatment of epithelial ovarian cancer? A.K. Crima, M. Rowlanda, R. Ruskina, J. Dvorakb, M. Greenwadeb, A. Waltera, J. Gillenb, K. Dingc, K.N. Moorec, C.C. Gundersonc. aThe University of Oklahoma, Stephenson Cancer Center, Oklahoma City, OK, USA, bUniversity of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, cThe University of Oklahoma, Oklahoma City, OK, USA
UN
CO
RR
EC
Objectives: Intraperitoneal (IP) chemotherapy for the treatment of epithelial ovarian cancer (EOC) has been shown to provide a substantial advantage in overall survival, and is now considered the standard of care. As the US population ages, evaluating these treatments, specifically for patients with this condition, is of utmost importance. This study aims to compare the toxicity and benefits of IP chemotherapy in patients of ages 70 years and older with those younger than 70 years. Methods: We performed a single institution retrospective review of patients diagnosed with stage IIA-IIIC EOC from 2000 to 2013 who received IP chemotherapy. Clinicopathologic characteristics were extracted, and survival was calculated. SAS version 9.3 was used for descriptive statistics and multivariate analyses. Results: A total of 133 patients were included, with 100 patients being younger than 70 years and 33 patients aged 70 years or older. Race, stage, histology, and performance status were similar. Residual disease did not differ (P = .23). All patients received a platinum/ taxane doublet for frontline chemotherapy. Clinical trial enrollment was similar (89% vs 90%, P = 1.00) despite age. In trial-enrolled patients, older patients received statistically fewer cycles of therapy (6.4 vs 5.8, P = .002) but had similar dose delays (0.9 vs 0.3, P = .17) and dose modifications (1.00 vs 0.93, P = .91). Median progressionfree survival (27 vs 31 months) and overall survival (71 and 62 months) were not statistically different. Grade 4 heme toxicities (P = 1.0), and grade 3 and higher non-heme toxicities (6.1% vs 6.7%, P = 1.0) were similar between groups. Although not statistically significant, neuropathy grade higher than 2 trended higher in the older group (100 vs 86%; P = .18). Upon multivariate analysis for overall survival, age less than 70 years (HR 0.697, 95% CI 0.36–1.26, P = .23) was not predictive, but stage (IIIC vs lower: HR 3.95, 95% CI