- Email: [email protected]
Abstract 9: Identification of molecular markers for targeted treatment of uterine sarcoma
282
Abstracts / Gynecologic Oncology 131 (2013) 277–285
Objectives: Pegylated liposomal doxorubicin (PLD) has been proven to have a reduced cardiotoxicity profile compared with doxorubicin, but recommendations regarding routine evaluation of cardiac function have not been published. The objectives of this study were to determine the cardiac safety of high cumulative doses of PLD in patients with gynecologic malignancies and the need for routine evaluation of LVEF. Methods: Data were collected for all patients treated with PLD with at least one evaluation of LVEF during treatment with either MUGA scan or echocardiogram from January 2006 to May 2012. Evaluation of LVEF was used to detect PLD-related cardiotoxicity. An initial evaluation of LVEF was performed along with repeat evaluations at regular intervals or for clinical signs of cardiotoxicity. Cardiotoxicity was defined as a decline in LVEF of greater than 10% compared to initial measurements. Statistical analysis was performed using Chi-square test for categorical data and analysis of variance (ANOVA) for continuous data. All analyses were performed using SAS Version 9.2 software (Statistical Analysis System, Cary, NC). Results: A total of 141 patients were included. Measurements of LVEF were obtained on 125 patients before initiation of treatment with PLD and repeated on 48 patients during the course of therapy. The median cumulative dose was 200 mg/m2 (range 40 mg/m2 to 1775 mg/m2 over a range of 1–45 cycles). Twenty-two patients were treated with a cumulative dose of 500 mg/m2 or more, and 5 patients with 1000 mg/m2 or more. Ten patients (7%) had a reduction in LVEF of greater than 10% (only 5 decreased below 60%), 38 had no significant change or increase in LVEF throughout the duration of treatment, and 93 did not require a follow up evaluation of LVEF. The LVEFs of two patients dropped below 50% at cumulative doses of 1110 mg/m2 and 1670 mg/m2, one began with a baseline of 52%. Neither had a previous diagnosis of CHF or treatment with adriamycin. Notably, two patients had a previous diagnosis of CHF, and treatment of both of these patients resulted in a decrease in LVEF of greater than 10%. Conclusions: Only one patient in our study had a clinically significant decrease in LVEF at a cumulative dose of 1670 mg/m2. Our study suggests that PLD does not carry a significant risk of cardiotoxicity, as evidenced by the stability of LVEF even after treatment with large cumulative doses. Routine surveillance of LVEF does not seem to be necessary or cost effective.
doi:10.1016/j.ygyno.2013.04.038
Abstract 9: Identification of molecular markers for targeted treatment of uterine sarcoma J. Shank1, J. Rhode2, J. Liu1. 1University of Michigan, Ann Arbor, MI, USA, 2 Monarch Women's Cancer Center, Salt Lake City, UT, USA Objectives: Uterine sarcomas are rare and aggressive tumor types. Patients diagnosed with this disease often have poor clinical outcomes, despite multi-modal therapy. Because uterine sarcomas are not common, investigations into novel therapeutics for this disease have been limited. The aim of our study was to identify the expression of therapeutic targets using tissue microarrays in order to direct the exploration of molecularly targeted treatment. Methods: Tumor tissue was collected from 36 patients with uterine sarcomas (6 endometrial stromal sarcomas [ESS], 7 leiomyosarcomas [LMS], and 23 carcinosarcoma [CS]) who were evaluated at a single cancer center between 1996 and 2004. Tissue microarrays were constructed and expression of several molecular markers that are associated with targeted therapeutics in current use for other tumor types was assessed. Expression of VEGF, EGRF, c-Kit and HER-2 was investigated using immunohistochemistry. Immunostaining was evaluated by a gynecologic pathologist. Clinical outcomes including
demographic data, treatment modalities received, and overall survival were recorded. Results: The mean age of patients included in this study was 63 (range 35–91). Expression of VEGF, EGFR, c-KIT, and HER-2 was detected in 81%, 81%, 72%, and 14% of all uterine sarcomas examined respectively. VEGF was expressed in 17% of ESS (1/6), 86% of LMS (6/ 7), and 96% of CS (22/23). EGFR was expressed in 50% of ESS (3/6), 86% of LMS (6/7), and 87% of CS (20/23). Expression of c-KIT was seen in 50% of ESS (3/6), 57% of LMS (4/7), and 83% of CS (19/23). HER-2 expression was minimal in all tumor types (ESS 17% [1/6], no expression in any LMS samples, and CS 7% [4/23]). Conclusions: Our data suggests that anti-angiogenic therapy may have activity in uterine leiomyosarcomas and carcinosarcomas. Targeted therapy for EGFR may have significant effects in patients with LMS and CS. This finding may justify using monoclonal antibodies against EGFR (such as cetuximab) or small molecule inhibitors of EGFR (such as gefitinib) in patients with LMS and CS. c-KIT also may be a potential target in CS and further studies with imatinib may be justified. HER-2 is a poor therapeutic target in all three types of uterine sarcomas. These results provide rationale for the use of targeted therapy to improve outcomes for uterine sarcoma patients. doi:10.1016/j.ygyno.2013.04.039
Abstract 10: Comparison of outcomes in patients undergoing rectosigmoid resection: End colostomy versus reanastomosis M. Quimper, J. Lesnock, S. Beriwal, T. Krivak, A. Olawaiye, J. Lin, P. Sukumvanich. Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA Objectives: Patients who undergo rectosigmoid resection at the time of initial debulking have an increased risk for bowel leak following primary reanastomosis, which may delay the start of chemotherapy. The aim of this study is to compare outcomes and time to chemotherapy in patients undergoing a cytoreductive surgery that included a rectosigmoid resection with either reanastomosis versus end colostomy. Methods: Following IRB approval, a retrospective chart review of consecutive patients who underwent a rectosigmoid resection as part of a cytoreductive surgery for a gynecologic malignancy between 2002 and 2012 at a single institution. Perioperative and follow-up data were collected. Chi-square, Fisher's exact test and Mann–Whitney U test were used for univariate analysis where applicable. Binary logistic regression was used for multivariate analysis. Results: Of the 144 patients who underwent a rectosigmoid resection, 61 (42%) patients had creation of an end colostomy (EC), and 83 (58%) had primary reanastomosis (RA). The median time to chemotherapy for the EC group was 41 days, compared to 43 days for the RA group (p = 0.43). In the RA group, eight (9.9%) patients experienced a bowel leak, compared to zero in the EC group (p b 0.05). Postoperative infection rates were 27.9% and 30.1% for the EC and RA groups, respectively (p = 0.72). Fistula formation occurred in five (6%) of patients in the RA group compared with zero patients in the EC group (p = 0.07). Risks of any surgical complication were 59.3% and 40.5% in patients in whom hemostatic products (such as fibrin sealant) were and weren't used, respectively (p b 0.05). Median estimated blood loss for the RA group was 600 mL, compared to 1000 mL in the EC group (p b 0.005). No factor was independently predictive of infectious/leak complications. Age at surgery (hazard ratio 1.102 [95% CI 1.003–1.212] per year, p b 0.05) and use of hemostatic products (hazard ratio 7.988 [1.186–53.819], p b 0.05) were independently associated with experiencing a surgical complication on multivariate analysis.
Abstracts / Gynecologic Oncology 131 (2013) 277–285
Objectives: Pegylated liposomal doxorubicin (PLD) has been proven to have a reduced cardiotoxicity profile compared with doxorubicin, but recommendations regarding routine evaluation of cardiac function have not been published. The objectives of this study were to determine the cardiac safety of high cumulative doses of PLD in patients with gynecologic malignancies and the need for routine evaluation of LVEF. Methods: Data were collected for all patients treated with PLD with at least one evaluation of LVEF during treatment with either MUGA scan or echocardiogram from January 2006 to May 2012. Evaluation of LVEF was used to detect PLD-related cardiotoxicity. An initial evaluation of LVEF was performed along with repeat evaluations at regular intervals or for clinical signs of cardiotoxicity. Cardiotoxicity was defined as a decline in LVEF of greater than 10% compared to initial measurements. Statistical analysis was performed using Chi-square test for categorical data and analysis of variance (ANOVA) for continuous data. All analyses were performed using SAS Version 9.2 software (Statistical Analysis System, Cary, NC). Results: A total of 141 patients were included. Measurements of LVEF were obtained on 125 patients before initiation of treatment with PLD and repeated on 48 patients during the course of therapy. The median cumulative dose was 200 mg/m2 (range 40 mg/m2 to 1775 mg/m2 over a range of 1–45 cycles). Twenty-two patients were treated with a cumulative dose of 500 mg/m2 or more, and 5 patients with 1000 mg/m2 or more. Ten patients (7%) had a reduction in LVEF of greater than 10% (only 5 decreased below 60%), 38 had no significant change or increase in LVEF throughout the duration of treatment, and 93 did not require a follow up evaluation of LVEF. The LVEFs of two patients dropped below 50% at cumulative doses of 1110 mg/m2 and 1670 mg/m2, one began with a baseline of 52%. Neither had a previous diagnosis of CHF or treatment with adriamycin. Notably, two patients had a previous diagnosis of CHF, and treatment of both of these patients resulted in a decrease in LVEF of greater than 10%. Conclusions: Only one patient in our study had a clinically significant decrease in LVEF at a cumulative dose of 1670 mg/m2. Our study suggests that PLD does not carry a significant risk of cardiotoxicity, as evidenced by the stability of LVEF even after treatment with large cumulative doses. Routine surveillance of LVEF does not seem to be necessary or cost effective.
doi:10.1016/j.ygyno.2013.04.038
Abstract 9: Identification of molecular markers for targeted treatment of uterine sarcoma J. Shank1, J. Rhode2, J. Liu1. 1University of Michigan, Ann Arbor, MI, USA, 2 Monarch Women's Cancer Center, Salt Lake City, UT, USA Objectives: Uterine sarcomas are rare and aggressive tumor types. Patients diagnosed with this disease often have poor clinical outcomes, despite multi-modal therapy. Because uterine sarcomas are not common, investigations into novel therapeutics for this disease have been limited. The aim of our study was to identify the expression of therapeutic targets using tissue microarrays in order to direct the exploration of molecularly targeted treatment. Methods: Tumor tissue was collected from 36 patients with uterine sarcomas (6 endometrial stromal sarcomas [ESS], 7 leiomyosarcomas [LMS], and 23 carcinosarcoma [CS]) who were evaluated at a single cancer center between 1996 and 2004. Tissue microarrays were constructed and expression of several molecular markers that are associated with targeted therapeutics in current use for other tumor types was assessed. Expression of VEGF, EGRF, c-Kit and HER-2 was investigated using immunohistochemistry. Immunostaining was evaluated by a gynecologic pathologist. Clinical outcomes including
demographic data, treatment modalities received, and overall survival were recorded. Results: The mean age of patients included in this study was 63 (range 35–91). Expression of VEGF, EGFR, c-KIT, and HER-2 was detected in 81%, 81%, 72%, and 14% of all uterine sarcomas examined respectively. VEGF was expressed in 17% of ESS (1/6), 86% of LMS (6/ 7), and 96% of CS (22/23). EGFR was expressed in 50% of ESS (3/6), 86% of LMS (6/7), and 87% of CS (20/23). Expression of c-KIT was seen in 50% of ESS (3/6), 57% of LMS (4/7), and 83% of CS (19/23). HER-2 expression was minimal in all tumor types (ESS 17% [1/6], no expression in any LMS samples, and CS 7% [4/23]). Conclusions: Our data suggests that anti-angiogenic therapy may have activity in uterine leiomyosarcomas and carcinosarcomas. Targeted therapy for EGFR may have significant effects in patients with LMS and CS. This finding may justify using monoclonal antibodies against EGFR (such as cetuximab) or small molecule inhibitors of EGFR (such as gefitinib) in patients with LMS and CS. c-KIT also may be a potential target in CS and further studies with imatinib may be justified. HER-2 is a poor therapeutic target in all three types of uterine sarcomas. These results provide rationale for the use of targeted therapy to improve outcomes for uterine sarcoma patients. doi:10.1016/j.ygyno.2013.04.039
Abstract 10: Comparison of outcomes in patients undergoing rectosigmoid resection: End colostomy versus reanastomosis M. Quimper, J. Lesnock, S. Beriwal, T. Krivak, A. Olawaiye, J. Lin, P. Sukumvanich. Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA Objectives: Patients who undergo rectosigmoid resection at the time of initial debulking have an increased risk for bowel leak following primary reanastomosis, which may delay the start of chemotherapy. The aim of this study is to compare outcomes and time to chemotherapy in patients undergoing a cytoreductive surgery that included a rectosigmoid resection with either reanastomosis versus end colostomy. Methods: Following IRB approval, a retrospective chart review of consecutive patients who underwent a rectosigmoid resection as part of a cytoreductive surgery for a gynecologic malignancy between 2002 and 2012 at a single institution. Perioperative and follow-up data were collected. Chi-square, Fisher's exact test and Mann–Whitney U test were used for univariate analysis where applicable. Binary logistic regression was used for multivariate analysis. Results: Of the 144 patients who underwent a rectosigmoid resection, 61 (42%) patients had creation of an end colostomy (EC), and 83 (58%) had primary reanastomosis (RA). The median time to chemotherapy for the EC group was 41 days, compared to 43 days for the RA group (p = 0.43). In the RA group, eight (9.9%) patients experienced a bowel leak, compared to zero in the EC group (p b 0.05). Postoperative infection rates were 27.9% and 30.1% for the EC and RA groups, respectively (p = 0.72). Fistula formation occurred in five (6%) of patients in the RA group compared with zero patients in the EC group (p = 0.07). Risks of any surgical complication were 59.3% and 40.5% in patients in whom hemostatic products (such as fibrin sealant) were and weren't used, respectively (p b 0.05). Median estimated blood loss for the RA group was 600 mL, compared to 1000 mL in the EC group (p b 0.005). No factor was independently predictive of infectious/leak complications. Age at surgery (hazard ratio 1.102 [95% CI 1.003–1.212] per year, p b 0.05) and use of hemostatic products (hazard ratio 7.988 [1.186–53.819], p b 0.05) were independently associated with experiencing a surgical complication on multivariate analysis.