- Email: [email protected]
Inhibition of HIF1a promotes paclitaxel efficacy in CD133 + ovarian carcinoma cells
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Abstracts / Gynecologic Oncology 133 (2014) 2–207
(52%) (P = 0.33). Of the 88 patients (44%) who received b6 IP cycles, the most common reasons were: poor performance status (17 [19%]), gastrointestinal symptoms/dehydration (10 [11%]), and renal/metabolic toxicity (9 [10%]). Conclusions: In our study, we did not detect a significant survival difference between patients who received 1 to 2, 3 to 4, or 5 to 6 cycles of IV/IP chemotherapy. Patients who receive b6 cycles of IV/IP chemotherapy as part of their postoperative treatment may still have a survival benefit. doi:10.1016/j.ygyno.2014.03.259
240 - Poster Session A Venous thromboembolism carries a particularly grave prognosis with epithelial ovarian cancer C.C. Gunderson1, E.D. Thomas2, K.N. Slaughter1, R. Farrell1, K. Ding1, J.K. Lauer1, L. Perry1, D.S. McMeekin1, K.N. Moore1. 1The University of Oklahoma, Oklahoma City, OK, USA, 2Stephenson Cancer Center, The University of Oklahoma, Oklahoma City, OK, USA. Objectives: To analyze survival with preoperative vs postoperative venous thromboembolism (VTE) in patients with epithelial ovarian cancer (EOC). Methods: A retrospective chart review was performed consisting of patients treated for stage I–IV EOC from January 1996 to June 2011. Demographic, clinicopathologic, and treatment characteristics were recorded. VTE was dichotomized as preoperative (pre-op) or postoperative (post-op). SAS 9.2 was used for statistical analyses. Results: Among the 586 patients who met study criteria, the median age was 63 years (range, 17–94 years), 88% were white, and 87.9% had performance status = 0 at diagnosis. Median body mass index (BMI) was 27.1 (range, 13.7–67.0). Underlying hypertension was present in 42.3%, and 10.8% had diabetes mellitus. Most (68.7%) had high-grade serous histology and advanced-stage (III/IV) disease (61.6%) and underwent lymphadenectomy (71.2%). Four percent had a pre-op VTE and 13.7% had a post-op VTE. Of the patients with pre-op VTE, 62% had pulmonary emboli vs 83% of patients with postop VTE. Platelet count did not differ with pre-op (P = 0.26) or postop (P = 0.06) VTE, but CA-125 levels were higher in patients with both pre-op (median 478 U/mL vs 242 U/mL, P = 0.046) and post-op VTE (473 U/mL vs 227 U/mL, P = 0.0015) as compared to patients without VTE. Patients with post-op VTE were more likely to have had any radical procedure (49.4% vs 24.7%, P b 0.001) as well as individual radical procedures such as colon resection (40.3% vs 16.6%, P b 0.0001), splenectomy (11.8% vs 3.9%, P = 0.008), and diaphragm stripping (14.3% vs 3.7%, P b 0.001). Pre-op VTE was unrelated to PFS (P = 0.11) but was associated with attenuated OS (median 19.7 months vs 66.0 months; HR 2.5, 95% CI 1.5–4.3, P = 0.0007). Post-op VTE was associated with both shortened PFS (median 14.4 months vs 25.9 months; HR 1.5, 95% CI 1.2–2.0, P = 0.002) and OS (median 47.6 months vs 83.9 months; HR 1.6, 95% CI 1.2–2.2, P = 0.004). Upon multivariate analysis adjusting for age, stage, histology, performance status, and residual disease, pre-op VTE remained predictive of OS (P = 0.01) but not PFS, although postop VTE was associated with shorter PFS (P = 0.004) and OS (P = 0.006). Conclusions: Both pre-op and post-op VTE appear to have a detrimental effect on OS of patients with EOC. However, it is unclear whether VTE is an inherent poor prognostic marker or if improved VTE prophylaxis and treatment may enable similar survival to patients without these events. doi:10.1016/j.ygyno.2014.03.260
241 - Poster Session A Solitomab, an EpCAM/CD3 bispecific antibody (BiTE®), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo D.P. English, C.L. Schwab, D.M. Roque, S. Bellone, E.S. Ratner, D.A. Silasi, M. Azodi, P.E. Schwartz, T.J. Rutherford, A. Santin. Yale University School of Medicine, New Haven, CT, USA. Objectives: Chemotherapy-resistant ovarian cancer remains an incurable disease. Solitomab is a novel bispecific single-chain antibody that targets the epithelial antigen EpCAM on tumor cells and also contains a CD3-binding region. We evaluated the in vitro activity of solitomab against multiple primary chemotherapyresistant epithelial ovarian carcinoma cell lines and malignant tumor cells in ascitic fluid. Methods: EpCAM expression was evaluated by real-time polymerase chain reaction (RT-PCR) and flow cytometry in 10 primary ovarian serous (OSC) cell lines and 10 fresh ovarian tumor cell cultures from ascitic fluids collected from patients with chemotherapy-resistant disease. The potential activity of solitomab against Ep-CAM/TROP-1positive tumor cells was evaluated by flow cytometry, proliferation, and 4-hour chromium-release cell-mediated cytotoxicity assays. Results: High expression of Ep-CAM/TROP-1 was detected by RT-PCR and flow cytometry in N90% of the ovarian tumors tested. Ep-CAM/ TROP-1-positive chemotherapy-resistant ovarian cancer cell lines were found highly resistant to natural killer cell-mediated killing after exposure to peripheral blood lymphocytes (PBL) in 4-hour chromium-release assays (mean killing ± SEM, 3.48% ± 0.62%; range, 0% to 12.7%). In contrast, after incubation with solitomab, Ep-CAM/TROP-1-positive chemotherapy-resistant ovarian cancer cells become highly sensitive to T-cell cytotoxicity (mean killing ± SEM of 28.2% ± 2.05%; range, 10% to 50.7%; P b 0.0001) by PBL. No killing was noted after incubation of EpCAM-positive cell lines with control BiTE. Ex vivo incubation for 96 h of autologous tumor associated lymphocytes (TAL) with EpCAM-expressing malignant cells in unmanipulated ascitic fluid with solitomab resulted in a significant increase in TAL expression of the T-cell activation markers CD25 (interleukin-2 receptor alpha) and human leucocyte antigen (HLA)-DR, increased secretion of interferon-gamma, and proliferation of CD8+ TAL (P = 0.01) as well as a dramatic reduction in the number of viable ovarian tumor cells in the ascitic fluid. Conclusions: Solitomab may represent a novel, potentially highly effective targeted agent for the treatment of chemotherapy-resistant/ refractory ovarian cancer patients overexpressing Ep-CAM/TROP-1. doi:10.1016/j.ygyno.2014.03.261
242 - Poster Session A Inhibition of HIF1a promotes paclitaxel efficacy in CD133+ ovarian carcinoma cells T. Okamoto1, Z. Huang1, R. Whitaker1, I. Konishi2, A. Berchuck1, S.K. Murphy1. 1Duke University, Durham, NC, USA, 2Kyoto University, Kyoto, Japan. Objectives: The cell surface protein CD133 demarcates an ovarian cancer-initiating cell (CIC) population. CD133+ cells are chemoresistant relative to CD133− ovarian cancer cells and are enriched in recurrent ovarian cancer. Our objective was to determine if metabolic characterization of CD133+ vs CD133− cells could be used to identify novel CD133+ cell targets for therapy. Methods: We analyzed gene expression microarray data from 34 ovarian cell lines for the proportion of CD133+ cells that was known. 41M, SKOV8, OVCAR4 ovarian cancer cell lines were sorted into CD133+ and CD133– subpopulations (n = 4 replicates) by flow
Abstracts / Gynecologic Oncology 133 (2014) 2–207
cytometry, and metabolic profiling of these cells was performed by Metabolon, Inc. (Durham, NC). The in vitro median inhibition concentrations for paclitaxel and/or noscapine (IC50 values) were determined and the Combination Index (CI) was calculated to determine if there is an additive, synergistic, or antagonistic effect between drugs. Results: Gene set enrichment analysis showed enrichment of CD133+ vs CD133- cells with HIF1A target genes (FDR q = 0.078). By metabolic profiling, trans-4 hydroxyproline (a product of HIF1A hydroxylation in the pathway leading to HIF1A degradation) was consistently decreased in CD133+ vs CD133– cells, approaching significance for 41M cells (P = 0.121). These results suggest that the ability to sustain higher levels of HIF1A in CD133+ cells may be due to hindered HIF1A degradation. Moreover, glucose and glycolytic metabolites were elevated in CD133+ vs CD133- OVCAR4 cells (0.1 b P b 0.2). CD133+ cells were more resistant to paclitaxel than their CD133− counterparts (IC50: 4.20 nM vs. 3.79 nM, P = 0.013). Treatment of these cells with the HIF1A inhibitor noscapine reduced HIF1A mRNA expression by 53.51%. Combined treatment with paclitaxel and noscapine was synergistic (CI 0.46). Conclusions: HIF1A-related metabolic differences along with differences in glucose uptake and utilization may be hallmarks of an ovarian cancer stem cell phenotype. Our results suggest that the HIF1A pathway is a potential therapeutic target in CD133+ CIC cells.
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the CT control group was associated with a worse prognosis with an HR of 1.95 (95% CI 1.015–3.761, P = 0.045) compared to the PET scan group. Conclusions: The use of PET scans in the evaluation of ovarian, PP, and fallopian tube CA patients may be associated with improved OS compared to patients who only undergo CT scans. Larger studies are needed to evaluate the role of PET scans in ovarian cancer.
doi:10.1016/j.ygyno.2014.03.263 doi:10.1016/j.ygyno.2014.03.262
243 - Poster Session A The utilization of positron emission tomography (PET) scans in ovarian, fallopian tube, and primary peritoneal carcinoma patients may be associated with improved overall survival N. Rasool, Y. Wang, R.K. Hanna, T.E. Buekers, A.R. Munkarah, S.H. Alford. Henry Ford Health System, Detroit, MI, USA. Objectives: To evaluate the practice patterns and use of positron emission tomography (PET) scans in patients with ovarian, primary peritoneal (PP), and fallopian tube carcinoma (CA) during treatment and surveillance vs routine CT scans alone as a prognostic factor for overall survival. Methods: A retrospective analysis of women who underwent a PET scan at any point during their course of treatment or surveillance for ovarian, PP, and fallopian tube CA was performed and compared to patients who underwent CT scans only. Univariate analysis was performed using the Wilcoxon and chi-square tests. Kaplan–Meier and Cox proportional hazard regression was used for survival analysis. Results: A total of 174 PET scans were performed in 58 patients. However, 19 of these patients had a diagnosis of another malignancy and were excluded from analysis. Of the remaining 39 patients, 120 PET scans were performed for an average of 3 PET scans/patient. The majority of PET scans were ordered by medical oncologists (75%), followed by gynecologic oncologists (16%), radiation oncologists (7%), and nononcologic physicians (3%). The main reasons for obtaining a PET study were to evaluate treatment response (45%), surveillance (28%), followup CT findings (18%), and evaluate symptoms/increasing CA-125 (8%). On further analysis, the 39 PET scan patients were compared to an equal number of matched CT control patients. There were no differences in age, histology, stage, grade, or debulking status between the PET and the CT control group. However, on Kaplan–Meier evaluation, there was a statistically significant difference in overall survival in those patients who underwent a PET scan at some point during their treatment or surveillance (overall survival [OS] = 75 months) vs those patients who only had CT scans for evaluation (OS = 43 months, P = 0.05) (Fig. 1). Controlling for age, histology, stage, grade, and debulking status, Cox regression was applied to assess the effect of PET and CT on OS. Similarly,
244 - Poster Session A Prognostic factors for overall survival in recurrent ovarian, fallopian tube, and peritoneal cancer patients treated with bevacizumab: A multisite study M.D. Dao1, E. Zsiros2, R.R. Urban1, H.J. Gray1, H.K. Tamimi1, B.A. Goff1, J.L. Tanyi2, J.B. Liao3. 1University of Washington Medical Center, Seattle, WA, USA, 2University of Pennsylvania, Philadelphia, PA, USA, 3University of Washington, Seattle, WA, USA. Objectives: To determine prognostic factors for overall survival (OS) in patients treated with bevacizumab (BEV) for recurrent ovarian, fallopian tube, and peritoneal cancers. Methods: A multisite retrospective review of patients treated with BEV for recurrent ovarian, fallopian tube, or peritoneal cancer from 2001 to 2012 was performed. Age at diagnosis, stage, histology, grade, surgical outcome, primary platinum response, number of chemotherapy regimens after primary adjuvant chemotherapy but prior to BEV treatment, interval from completion of primary adjuvant chemotherapy to starting BEV treatment, and survival outcomes were abstracted. Cox proportional hazards regression was used to identify independent prognostic factors for OS (from BEV treatment start), using log-rank test. Results: Of 161 patients identified, 131 consecutive women with complete medical records were available for analysis. Patients were treated with BEV alone (n = 6) or with concurrent cytotoxic chemotherapy (n = 125). A total of 107 deaths (82%) were identified, with median OS of 23.8 months. Factors associated with improved OS included age b60 years (n = 66) at primary diagnosis (median 33.1 months vs 16.9 months, P = 0.021), receiving 1 cytotoxic chemotherapy regimen (n = 23) for recurrence prior to initiation of BEV (median 33.7 months vs 22.2 months for 2 regimens vs. 20.1 months for ≥3 regimens vs 18.8 months for no regimen, P = 0.018), and having platinum-sensitive disease (n = 74) following initial adjuvant chemotherapy (median 34.6 months vs 13 months, P b 0.001). Primary platinum sensitivity was an independent predictor of improved OS (P b 0.001). Receipt of 1 prior chemotherapy regimen, but not 0, 2, 3, or more prior regimens, was an independent predictor of improved OS (P = 0.025), despite no significant difference in proportions of platinum-
Abstracts / Gynecologic Oncology 133 (2014) 2–207
(52%) (P = 0.33). Of the 88 patients (44%) who received b6 IP cycles, the most common reasons were: poor performance status (17 [19%]), gastrointestinal symptoms/dehydration (10 [11%]), and renal/metabolic toxicity (9 [10%]). Conclusions: In our study, we did not detect a significant survival difference between patients who received 1 to 2, 3 to 4, or 5 to 6 cycles of IV/IP chemotherapy. Patients who receive b6 cycles of IV/IP chemotherapy as part of their postoperative treatment may still have a survival benefit. doi:10.1016/j.ygyno.2014.03.259
240 - Poster Session A Venous thromboembolism carries a particularly grave prognosis with epithelial ovarian cancer C.C. Gunderson1, E.D. Thomas2, K.N. Slaughter1, R. Farrell1, K. Ding1, J.K. Lauer1, L. Perry1, D.S. McMeekin1, K.N. Moore1. 1The University of Oklahoma, Oklahoma City, OK, USA, 2Stephenson Cancer Center, The University of Oklahoma, Oklahoma City, OK, USA. Objectives: To analyze survival with preoperative vs postoperative venous thromboembolism (VTE) in patients with epithelial ovarian cancer (EOC). Methods: A retrospective chart review was performed consisting of patients treated for stage I–IV EOC from January 1996 to June 2011. Demographic, clinicopathologic, and treatment characteristics were recorded. VTE was dichotomized as preoperative (pre-op) or postoperative (post-op). SAS 9.2 was used for statistical analyses. Results: Among the 586 patients who met study criteria, the median age was 63 years (range, 17–94 years), 88% were white, and 87.9% had performance status = 0 at diagnosis. Median body mass index (BMI) was 27.1 (range, 13.7–67.0). Underlying hypertension was present in 42.3%, and 10.8% had diabetes mellitus. Most (68.7%) had high-grade serous histology and advanced-stage (III/IV) disease (61.6%) and underwent lymphadenectomy (71.2%). Four percent had a pre-op VTE and 13.7% had a post-op VTE. Of the patients with pre-op VTE, 62% had pulmonary emboli vs 83% of patients with postop VTE. Platelet count did not differ with pre-op (P = 0.26) or postop (P = 0.06) VTE, but CA-125 levels were higher in patients with both pre-op (median 478 U/mL vs 242 U/mL, P = 0.046) and post-op VTE (473 U/mL vs 227 U/mL, P = 0.0015) as compared to patients without VTE. Patients with post-op VTE were more likely to have had any radical procedure (49.4% vs 24.7%, P b 0.001) as well as individual radical procedures such as colon resection (40.3% vs 16.6%, P b 0.0001), splenectomy (11.8% vs 3.9%, P = 0.008), and diaphragm stripping (14.3% vs 3.7%, P b 0.001). Pre-op VTE was unrelated to PFS (P = 0.11) but was associated with attenuated OS (median 19.7 months vs 66.0 months; HR 2.5, 95% CI 1.5–4.3, P = 0.0007). Post-op VTE was associated with both shortened PFS (median 14.4 months vs 25.9 months; HR 1.5, 95% CI 1.2–2.0, P = 0.002) and OS (median 47.6 months vs 83.9 months; HR 1.6, 95% CI 1.2–2.2, P = 0.004). Upon multivariate analysis adjusting for age, stage, histology, performance status, and residual disease, pre-op VTE remained predictive of OS (P = 0.01) but not PFS, although postop VTE was associated with shorter PFS (P = 0.004) and OS (P = 0.006). Conclusions: Both pre-op and post-op VTE appear to have a detrimental effect on OS of patients with EOC. However, it is unclear whether VTE is an inherent poor prognostic marker or if improved VTE prophylaxis and treatment may enable similar survival to patients without these events. doi:10.1016/j.ygyno.2014.03.260
241 - Poster Session A Solitomab, an EpCAM/CD3 bispecific antibody (BiTE®), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo D.P. English, C.L. Schwab, D.M. Roque, S. Bellone, E.S. Ratner, D.A. Silasi, M. Azodi, P.E. Schwartz, T.J. Rutherford, A. Santin. Yale University School of Medicine, New Haven, CT, USA. Objectives: Chemotherapy-resistant ovarian cancer remains an incurable disease. Solitomab is a novel bispecific single-chain antibody that targets the epithelial antigen EpCAM on tumor cells and also contains a CD3-binding region. We evaluated the in vitro activity of solitomab against multiple primary chemotherapyresistant epithelial ovarian carcinoma cell lines and malignant tumor cells in ascitic fluid. Methods: EpCAM expression was evaluated by real-time polymerase chain reaction (RT-PCR) and flow cytometry in 10 primary ovarian serous (OSC) cell lines and 10 fresh ovarian tumor cell cultures from ascitic fluids collected from patients with chemotherapy-resistant disease. The potential activity of solitomab against Ep-CAM/TROP-1positive tumor cells was evaluated by flow cytometry, proliferation, and 4-hour chromium-release cell-mediated cytotoxicity assays. Results: High expression of Ep-CAM/TROP-1 was detected by RT-PCR and flow cytometry in N90% of the ovarian tumors tested. Ep-CAM/ TROP-1-positive chemotherapy-resistant ovarian cancer cell lines were found highly resistant to natural killer cell-mediated killing after exposure to peripheral blood lymphocytes (PBL) in 4-hour chromium-release assays (mean killing ± SEM, 3.48% ± 0.62%; range, 0% to 12.7%). In contrast, after incubation with solitomab, Ep-CAM/TROP-1-positive chemotherapy-resistant ovarian cancer cells become highly sensitive to T-cell cytotoxicity (mean killing ± SEM of 28.2% ± 2.05%; range, 10% to 50.7%; P b 0.0001) by PBL. No killing was noted after incubation of EpCAM-positive cell lines with control BiTE. Ex vivo incubation for 96 h of autologous tumor associated lymphocytes (TAL) with EpCAM-expressing malignant cells in unmanipulated ascitic fluid with solitomab resulted in a significant increase in TAL expression of the T-cell activation markers CD25 (interleukin-2 receptor alpha) and human leucocyte antigen (HLA)-DR, increased secretion of interferon-gamma, and proliferation of CD8+ TAL (P = 0.01) as well as a dramatic reduction in the number of viable ovarian tumor cells in the ascitic fluid. Conclusions: Solitomab may represent a novel, potentially highly effective targeted agent for the treatment of chemotherapy-resistant/ refractory ovarian cancer patients overexpressing Ep-CAM/TROP-1. doi:10.1016/j.ygyno.2014.03.261
242 - Poster Session A Inhibition of HIF1a promotes paclitaxel efficacy in CD133+ ovarian carcinoma cells T. Okamoto1, Z. Huang1, R. Whitaker1, I. Konishi2, A. Berchuck1, S.K. Murphy1. 1Duke University, Durham, NC, USA, 2Kyoto University, Kyoto, Japan. Objectives: The cell surface protein CD133 demarcates an ovarian cancer-initiating cell (CIC) population. CD133+ cells are chemoresistant relative to CD133− ovarian cancer cells and are enriched in recurrent ovarian cancer. Our objective was to determine if metabolic characterization of CD133+ vs CD133− cells could be used to identify novel CD133+ cell targets for therapy. Methods: We analyzed gene expression microarray data from 34 ovarian cell lines for the proportion of CD133+ cells that was known. 41M, SKOV8, OVCAR4 ovarian cancer cell lines were sorted into CD133+ and CD133– subpopulations (n = 4 replicates) by flow
Abstracts / Gynecologic Oncology 133 (2014) 2–207
cytometry, and metabolic profiling of these cells was performed by Metabolon, Inc. (Durham, NC). The in vitro median inhibition concentrations for paclitaxel and/or noscapine (IC50 values) were determined and the Combination Index (CI) was calculated to determine if there is an additive, synergistic, or antagonistic effect between drugs. Results: Gene set enrichment analysis showed enrichment of CD133+ vs CD133- cells with HIF1A target genes (FDR q = 0.078). By metabolic profiling, trans-4 hydroxyproline (a product of HIF1A hydroxylation in the pathway leading to HIF1A degradation) was consistently decreased in CD133+ vs CD133– cells, approaching significance for 41M cells (P = 0.121). These results suggest that the ability to sustain higher levels of HIF1A in CD133+ cells may be due to hindered HIF1A degradation. Moreover, glucose and glycolytic metabolites were elevated in CD133+ vs CD133- OVCAR4 cells (0.1 b P b 0.2). CD133+ cells were more resistant to paclitaxel than their CD133− counterparts (IC50: 4.20 nM vs. 3.79 nM, P = 0.013). Treatment of these cells with the HIF1A inhibitor noscapine reduced HIF1A mRNA expression by 53.51%. Combined treatment with paclitaxel and noscapine was synergistic (CI 0.46). Conclusions: HIF1A-related metabolic differences along with differences in glucose uptake and utilization may be hallmarks of an ovarian cancer stem cell phenotype. Our results suggest that the HIF1A pathway is a potential therapeutic target in CD133+ CIC cells.
99
the CT control group was associated with a worse prognosis with an HR of 1.95 (95% CI 1.015–3.761, P = 0.045) compared to the PET scan group. Conclusions: The use of PET scans in the evaluation of ovarian, PP, and fallopian tube CA patients may be associated with improved OS compared to patients who only undergo CT scans. Larger studies are needed to evaluate the role of PET scans in ovarian cancer.
doi:10.1016/j.ygyno.2014.03.263 doi:10.1016/j.ygyno.2014.03.262
243 - Poster Session A The utilization of positron emission tomography (PET) scans in ovarian, fallopian tube, and primary peritoneal carcinoma patients may be associated with improved overall survival N. Rasool, Y. Wang, R.K. Hanna, T.E. Buekers, A.R. Munkarah, S.H. Alford. Henry Ford Health System, Detroit, MI, USA. Objectives: To evaluate the practice patterns and use of positron emission tomography (PET) scans in patients with ovarian, primary peritoneal (PP), and fallopian tube carcinoma (CA) during treatment and surveillance vs routine CT scans alone as a prognostic factor for overall survival. Methods: A retrospective analysis of women who underwent a PET scan at any point during their course of treatment or surveillance for ovarian, PP, and fallopian tube CA was performed and compared to patients who underwent CT scans only. Univariate analysis was performed using the Wilcoxon and chi-square tests. Kaplan–Meier and Cox proportional hazard regression was used for survival analysis. Results: A total of 174 PET scans were performed in 58 patients. However, 19 of these patients had a diagnosis of another malignancy and were excluded from analysis. Of the remaining 39 patients, 120 PET scans were performed for an average of 3 PET scans/patient. The majority of PET scans were ordered by medical oncologists (75%), followed by gynecologic oncologists (16%), radiation oncologists (7%), and nononcologic physicians (3%). The main reasons for obtaining a PET study were to evaluate treatment response (45%), surveillance (28%), followup CT findings (18%), and evaluate symptoms/increasing CA-125 (8%). On further analysis, the 39 PET scan patients were compared to an equal number of matched CT control patients. There were no differences in age, histology, stage, grade, or debulking status between the PET and the CT control group. However, on Kaplan–Meier evaluation, there was a statistically significant difference in overall survival in those patients who underwent a PET scan at some point during their treatment or surveillance (overall survival [OS] = 75 months) vs those patients who only had CT scans for evaluation (OS = 43 months, P = 0.05) (Fig. 1). Controlling for age, histology, stage, grade, and debulking status, Cox regression was applied to assess the effect of PET and CT on OS. Similarly,
244 - Poster Session A Prognostic factors for overall survival in recurrent ovarian, fallopian tube, and peritoneal cancer patients treated with bevacizumab: A multisite study M.D. Dao1, E. Zsiros2, R.R. Urban1, H.J. Gray1, H.K. Tamimi1, B.A. Goff1, J.L. Tanyi2, J.B. Liao3. 1University of Washington Medical Center, Seattle, WA, USA, 2University of Pennsylvania, Philadelphia, PA, USA, 3University of Washington, Seattle, WA, USA. Objectives: To determine prognostic factors for overall survival (OS) in patients treated with bevacizumab (BEV) for recurrent ovarian, fallopian tube, and peritoneal cancers. Methods: A multisite retrospective review of patients treated with BEV for recurrent ovarian, fallopian tube, or peritoneal cancer from 2001 to 2012 was performed. Age at diagnosis, stage, histology, grade, surgical outcome, primary platinum response, number of chemotherapy regimens after primary adjuvant chemotherapy but prior to BEV treatment, interval from completion of primary adjuvant chemotherapy to starting BEV treatment, and survival outcomes were abstracted. Cox proportional hazards regression was used to identify independent prognostic factors for OS (from BEV treatment start), using log-rank test. Results: Of 161 patients identified, 131 consecutive women with complete medical records were available for analysis. Patients were treated with BEV alone (n = 6) or with concurrent cytotoxic chemotherapy (n = 125). A total of 107 deaths (82%) were identified, with median OS of 23.8 months. Factors associated with improved OS included age b60 years (n = 66) at primary diagnosis (median 33.1 months vs 16.9 months, P = 0.021), receiving 1 cytotoxic chemotherapy regimen (n = 23) for recurrence prior to initiation of BEV (median 33.7 months vs 22.2 months for 2 regimens vs. 20.1 months for ≥3 regimens vs 18.8 months for no regimen, P = 0.018), and having platinum-sensitive disease (n = 74) following initial adjuvant chemotherapy (median 34.6 months vs 13 months, P b 0.001). Primary platinum sensitivity was an independent predictor of improved OS (P b 0.001). Receipt of 1 prior chemotherapy regimen, but not 0, 2, 3, or more prior regimens, was an independent predictor of improved OS (P = 0.025), despite no significant difference in proportions of platinum-