- Email: [email protected]
Neoadjuvant chemotherapy reduces operative morbidity without effecting time to recurrence in advanced stage epithelial ovarian cancer
Abstracts / Gynecologic Oncology 137 (2015) 92–179
287 - Poster Session Fallopian tube detection in ovarian cancer screening with transvaginal ultrasonography J. Lefringhousea, E.J. Pavlika, E. Newardb, F.R. Uelandb, L.A. Baldwinb, R.W. Millerb, C.P. Desimoneb, J.R. Vannagellb. aUniversity of Kentucky, Lexington, KY, USA, bUniversity of Kentucky Medical Center, Lexington, KY, USA Objectives: There is increasing evidence implicating the fallopian tube as the origin of many ovarian malignancies (Clin Obstet Gynecol. 2012;55:24–35). Our aim was to examine the feasibility of visualizing the fallopian tube as part of ovarian cancer detection. Methods: The Kentucky Ovarian Cancer Screening Program evaluated 549 asymptomatic women, ages 26 to 85 years, using transvaginal ultrasonography. Observed ultrasonographic findings included visualization vs. non-visualization, dimensions, and volume of fallopian tubes and ovaries. Chi square analysis was performed. Results: There were no significant differences between women who had one or both fallopian tubes visualized vs. not visualized with respect to age (63.5 + 0.4 years), body mass index (26.2 + 0.2), or parity (2.1 + 0.05). A fallopian tube was detected and its volume calculated in 77.2% of women examined compared to 82.7% for ovaries (P b 0.05). When the ovary was visualized, the fallopian tube was identified 85% of the time. In this cohort, the non-visualized rate for ovaries was less than for fallopian tubes (22.8% vs. 17.5%, P b 0.05) (Table). Conclusions: The fallopian tube can be regularly identified with transvaginal ultrasonography in a screening population, although the non-visualized rate is higher than for the ovary. Further study is needed to determine whether specific fallopian tube pathology can be detected and classified.
n Total women examined Women with no fallopian tubes visualized Women with no ovaries visualized Women with 1 or 2 fallopian tubes visualized Women with 1 or 2 ovaries visualized Women with both fallopian tubes visualized Women with both ovaries visualized P b 0.001 (visualization fallopian tubes vs. ovaries)
%
Mean vol (cm3)
Median (range)
P value
549 100.0% 0.6 + 0.02 0.5 (0.1-4) 125 22.8% – – 95
17.5% –
–
117
multidrug resistance (MDR) to conventional chemotherapy. Novel strategies to overcome MDR are needed to treat these patients. PNC27, derived from HDM-2 binding domain of p53, binds to HDM-2 in the cancer cell membrane, leading to formation of pores and rapid tumor cell necrosis. We sought to determine anticancer activity of this peptide in MDR ovarian cancer. Methods: A total of 5 × 104 MDR SKOV-3 human ovarian cancer cells were treated with PNC-27 and control PNC-29 peptide constructs. MTT was used to measure cell proliferation while lactate dehydrogenase (LDH) and caspase-3 assays were employed to define mechanism of cell death. Confocal microscopy determined site of anticancer activity. Results: PNC-27 induced N80% reduction in cell proliferation compared to control PNC-29 and untreated cells (P b 0.001). Rapid (4 h) cellular necrosis with a 2.5-fold increase in LDH (P b 0.001) occurred in a dose-dependent manner, while caspase-3 activity was undetectable in PNC-27-treated cells. Confocal microscopy was remarkable for co-localization of PNC-27 and HDM-2, which appeared exclusive to the cancer cell membrane. Conclusions: Our preliminary results demonstrated that PNC-27 binds to HDM-2 on SKOV-3 cells and induces rapid cellular necrosis. Using PNC-27 peptide to overcome MDR will be explored in additional ovarian cancer cell lines as well as murine models.
doi:10.1016/j.ygyno.2015.01.291
289 - Poster Session Neoadjuvant chemotherapy reduces operative morbidity without effecting time to recurrence in advanced stage epithelial ovarian cancer S.E. Taylor, J. Berger, K. Johnson, M.M. Boisen, M.B. Courtney-Brooks, P. Sukumvanich, J.L. Kelley III, M. Huang. Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA
P b 0.05
424
77.2% 0.6 + 0.02 0.5 (0.1–4)
454
82.7% 1.3 + 0.08 0.9 (0.1–46.4) P b 0.05
252
45.9% 0.6 + 0.02 0.5 (4)
349
63.6% 1.3 + 0.09 0.9 (0.1–46.4) P b 0.001 +SEM
doi:10.1016/j.ygyno.2015.01.290
288 - Poster Session Evaluating anti-cancer activity of a novel p53-derived peptide against multidrug resistant ovarian cancer M.F. Shaikha,b, D. Zimmermana,b, K. Davitta,b, E.M. Gleesona,b, P. Lovea,b, B.D. Babcocka,b, M.R. Pincusc, W.B. Bownea,b, S.D. Richarda,b, A.R. Desaia,b. aHahnemann University Hospital, Philadelphia, PA, USA, b Drexel University College of Medicine, Philadelphia, PA, USA, cSUNY Downstate, Brooklyn, NY, USA Objectives: Among the estimated 22,000 women diagnosed with ovarian cancer in the United States each year, many develop lethal
Objectives: Primary debulking surgery (PDS) is considered standard of care for advanced-stage epithelial ovarian cancer (EOC). The role of neoadjuvant chemotherapy (NACT) remains a topic of debate. The objective of this study was to compare the rate of optimal cytoreductive surgery and postoperative complications in patients undergoing primary vs. interval cytoreductive surgery and its effect on time to recurrence. Methods: A single-institution retrospective chart review of patients who underwent primary treatment for advanced EOC was performed. Cases of NACT followed by cytoreduction were identified and matched 1:1 by time of diagnosis to cases of PDS. Time to recurrence was defined as date of diagnosis to date of initiation of second-line chemotherapy and optimal cytoreduction was defined as residual disease b0.5 cm. Fisher's exact test and Mann–Whitney were used for statistical analysis. Results: From January 2007 to December 2012, 98 patients treated with NACT were identified and matched to 98 PDS patients. Demographic, clinicopathologic, and other variables are listed in Table 1. The rate of optimal cytoreduction was 87.8% and 51% in the NACT and PDS groups, respectively (P b 0.0001). Postoperative complications affected 34% of patients in the NACT group and 68% of patients in the PDS group (P b 0.0001). Time to recurrence was 16 months in both groups (P = 1). Conclusions: The use of NACT in the treatment of EOC does not affect the time to recurrence but does increase the rate of optimal cytoreductive surgery and decrease the number of postoperative complications. This indicates that the use of NACT does not adversely
118
Abstracts / Gynecologic Oncology 137 (2015) 92–179
affect time to recurrence but may decrease the perioperative morbidity associated with cytoreductive surgery.
Table 1 Demographic, clinicopathologic, and outcome data.
Age BMI Race White Black Other Unknown Primary site Ovarian Fallopian tube Primary peritoneal Unknown Histology Serous Endometrioid Mucinous Clear cell Other Debulking status Suboptimal N1 cm Optimal 0.5 cm–1 cm Optimal b 0.5 cm Optimal, microscopic Stage II III IV Missing Postoperative complication Time to recurrence
NACT
PDS
64.5 28.5 84 4 3 8
63.4 28 84 7 0 7
67 21 7 3
60 31 7 0
80 3 1 1 8
85 0 0 4 9
5 7 22 64
27 21 18 32
N/A
0 81 11 6
68% 16 months
34% 16 months
Neoadjuvant chemotherapy (NACT), primary debulking surgery (PDS).
doi:10.1016/j.ygyno.2015.01.292
290 - Poster Session Time to chemotherapy following surgical cytoreduction for epithelial ovarian cancer: Does neoadjuvant chemotherapy make a difference? M.M. Boisen, J. Berger, J. Phillips, S.E. Taylor, A. Peters, J.T. Comerci, R.P. Edwards, J.L. Kelley III, P. Sukumvanich, M. Huang. Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA Objectives: Neoadjuvant chemotherapy (NACT) prior to surgical cytoreduction for advanced epithelial ovarian cancer (EOC) is thought to have equivalent patient outcomes when compared to primary debulking (PDS). The NACT approach may reduce the need for morbid surgical procedures, shorten hospital stays, and shorten the interval to adjuvant therapy. We sought to determine whether NACT affects time to adjuvant chemotherapy following surgical cytoreduction. Methods: Institutional review board approval was obtained. Patients who underwent primary treatment for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers at our institution from January, 2007 to December, 2013 were included. NACT followed by cytoreduction and PDS cases were matched 1:1. Patient charts were abstracted for demographic information, treatment characteristics, and patient outcomes. Statistical tests were performed with Fisher's exact test and the Mann–Whitney test with P b 0.05 considered significant. Results: A total of 196 patients were identified, 98 in the NACT and PDS arms, respectively. Mean age in the NACT arm was 63.4 years and was 64.5 years in the PDS arm. There were 60 ovarian, 31
fallopian tube, and 7 primary peritoneal cancers in the PDS arm and 61 ovarian, 21 fallopian tube, and 7 primary peritoneal cancers in the NACT arm. The majority of patients (165 [84%]) had serous tumors. In the NACT arm, the median number of chemotherapy cycles prior to cytoreduction was 4 (range, 1–7). Seventy-one (72%) and 93 (95%) patients were optimally cytoreduced in the PDS and NAC groups, respectively. Thirty-three (34%) patients in the NACT arm had surgical complications as compared to 67 (68%) in the PDS group (P b 0.0001). Median time to initiation of adjuvant chemotherapy following cytoreduction in the NACT group was 34.0 days compared to 36.0 days in the PDS group. These differences were not statistically significant (P = 0.73). Conclusions: Time to initiation of chemotherapy did not differ between the two groups, despite fewer surgical complications in the NACT arm. Further work to assess how time to adjuvant chemotherapy affects overall outcomes is warranted.
doi:10.1016/j.ygyno.2015.01.293
291 - Poster Session Visceral adiposity associated with increased risk of death from ovarian cancer Y. Zhang, P. Allen, L.A. Meyer, C.C.L. Sun, K.M. Basen-Engquist, K.H. Lu, A.H. Klopp. The University of Texas MD Anderson Cancer Center, Houston, TX, USA Objectives: Central, or visceral, obesity increases the risk of developing ovarian cancer. The impact of visceral obesity on recurrence in women with ovarian cancer is unknown. We hypothesized that excess visceral adipose may increase the risk of recurrence in patients with ovarian cancer. Methods: The medical records of 185 patients with stage I–IV ovarian cancer who underwent initial surgery between January 1, 2001 and December 31, 2009 on a tumor banking protocol at our institution were reviewed. The thickness of perirenal adipose tissue, an established surrogate measure of visceral adiposity, was measured on computed tomography scans obtained within 6 months of initial diagnosis. Disease-free survival (DFS) and overall survival (OS) were computed using the Kaplan–Meier method and log-rank tests. Univariate and multivariate Cox proportional hazards' analyses were used to determine relationships between clinical variables and DFS and OS. Results: Patients with greater than the median thickness of perirenal adipose tissue (5 mm) had lower rates of DFS at 5 years (45.6% vs. 53.8%, P = 0.05). On univariate analysis, stage III or IV disease, treatment with neoadjuvant chemotherapy, elevated posttreatment CA-125, and N2 cm of residual disease was associated with lower DFS. Elevated body mass index was not associated with DFS. In multivariate analysis, N5 mm of perirenal adipose tissue was associated with a higher risk of death from ovarian cancer (HR = 1.37, 95% CI 1.03–1.82). Stage, residual disease, and treatment with neoadjuvant chemotherapy also remained associated with a lower DFS on multivariate analysis. Greater than 5 mm of perirenal adipose tissue was also independently predictive of a higher risk of death on multivariate analysis (HR = 1.46, 95% CI 1.08–1.98). Conclusions: Our data suggest that increased visceral adipose, but not body mass index, is associated with a higher risk of death from ovarian cancer. Strategies targeted at reducing visceral adipose tissue may improve outcomes in women who have been diagnosed with ovarian cancer.
doi:10.1016/j.ygyno.2015.01.294
287 - Poster Session Fallopian tube detection in ovarian cancer screening with transvaginal ultrasonography J. Lefringhousea, E.J. Pavlika, E. Newardb, F.R. Uelandb, L.A. Baldwinb, R.W. Millerb, C.P. Desimoneb, J.R. Vannagellb. aUniversity of Kentucky, Lexington, KY, USA, bUniversity of Kentucky Medical Center, Lexington, KY, USA Objectives: There is increasing evidence implicating the fallopian tube as the origin of many ovarian malignancies (Clin Obstet Gynecol. 2012;55:24–35). Our aim was to examine the feasibility of visualizing the fallopian tube as part of ovarian cancer detection. Methods: The Kentucky Ovarian Cancer Screening Program evaluated 549 asymptomatic women, ages 26 to 85 years, using transvaginal ultrasonography. Observed ultrasonographic findings included visualization vs. non-visualization, dimensions, and volume of fallopian tubes and ovaries. Chi square analysis was performed. Results: There were no significant differences between women who had one or both fallopian tubes visualized vs. not visualized with respect to age (63.5 + 0.4 years), body mass index (26.2 + 0.2), or parity (2.1 + 0.05). A fallopian tube was detected and its volume calculated in 77.2% of women examined compared to 82.7% for ovaries (P b 0.05). When the ovary was visualized, the fallopian tube was identified 85% of the time. In this cohort, the non-visualized rate for ovaries was less than for fallopian tubes (22.8% vs. 17.5%, P b 0.05) (Table). Conclusions: The fallopian tube can be regularly identified with transvaginal ultrasonography in a screening population, although the non-visualized rate is higher than for the ovary. Further study is needed to determine whether specific fallopian tube pathology can be detected and classified.
n Total women examined Women with no fallopian tubes visualized Women with no ovaries visualized Women with 1 or 2 fallopian tubes visualized Women with 1 or 2 ovaries visualized Women with both fallopian tubes visualized Women with both ovaries visualized P b 0.001 (visualization fallopian tubes vs. ovaries)
%
Mean vol (cm3)
Median (range)
P value
549 100.0% 0.6 + 0.02 0.5 (0.1-4) 125 22.8% – – 95
17.5% –
–
117
multidrug resistance (MDR) to conventional chemotherapy. Novel strategies to overcome MDR are needed to treat these patients. PNC27, derived from HDM-2 binding domain of p53, binds to HDM-2 in the cancer cell membrane, leading to formation of pores and rapid tumor cell necrosis. We sought to determine anticancer activity of this peptide in MDR ovarian cancer. Methods: A total of 5 × 104 MDR SKOV-3 human ovarian cancer cells were treated with PNC-27 and control PNC-29 peptide constructs. MTT was used to measure cell proliferation while lactate dehydrogenase (LDH) and caspase-3 assays were employed to define mechanism of cell death. Confocal microscopy determined site of anticancer activity. Results: PNC-27 induced N80% reduction in cell proliferation compared to control PNC-29 and untreated cells (P b 0.001). Rapid (4 h) cellular necrosis with a 2.5-fold increase in LDH (P b 0.001) occurred in a dose-dependent manner, while caspase-3 activity was undetectable in PNC-27-treated cells. Confocal microscopy was remarkable for co-localization of PNC-27 and HDM-2, which appeared exclusive to the cancer cell membrane. Conclusions: Our preliminary results demonstrated that PNC-27 binds to HDM-2 on SKOV-3 cells and induces rapid cellular necrosis. Using PNC-27 peptide to overcome MDR will be explored in additional ovarian cancer cell lines as well as murine models.
doi:10.1016/j.ygyno.2015.01.291
289 - Poster Session Neoadjuvant chemotherapy reduces operative morbidity without effecting time to recurrence in advanced stage epithelial ovarian cancer S.E. Taylor, J. Berger, K. Johnson, M.M. Boisen, M.B. Courtney-Brooks, P. Sukumvanich, J.L. Kelley III, M. Huang. Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA
P b 0.05
424
77.2% 0.6 + 0.02 0.5 (0.1–4)
454
82.7% 1.3 + 0.08 0.9 (0.1–46.4) P b 0.05
252
45.9% 0.6 + 0.02 0.5 (4)
349
63.6% 1.3 + 0.09 0.9 (0.1–46.4) P b 0.001 +SEM
doi:10.1016/j.ygyno.2015.01.290
288 - Poster Session Evaluating anti-cancer activity of a novel p53-derived peptide against multidrug resistant ovarian cancer M.F. Shaikha,b, D. Zimmermana,b, K. Davitta,b, E.M. Gleesona,b, P. Lovea,b, B.D. Babcocka,b, M.R. Pincusc, W.B. Bownea,b, S.D. Richarda,b, A.R. Desaia,b. aHahnemann University Hospital, Philadelphia, PA, USA, b Drexel University College of Medicine, Philadelphia, PA, USA, cSUNY Downstate, Brooklyn, NY, USA Objectives: Among the estimated 22,000 women diagnosed with ovarian cancer in the United States each year, many develop lethal
Objectives: Primary debulking surgery (PDS) is considered standard of care for advanced-stage epithelial ovarian cancer (EOC). The role of neoadjuvant chemotherapy (NACT) remains a topic of debate. The objective of this study was to compare the rate of optimal cytoreductive surgery and postoperative complications in patients undergoing primary vs. interval cytoreductive surgery and its effect on time to recurrence. Methods: A single-institution retrospective chart review of patients who underwent primary treatment for advanced EOC was performed. Cases of NACT followed by cytoreduction were identified and matched 1:1 by time of diagnosis to cases of PDS. Time to recurrence was defined as date of diagnosis to date of initiation of second-line chemotherapy and optimal cytoreduction was defined as residual disease b0.5 cm. Fisher's exact test and Mann–Whitney were used for statistical analysis. Results: From January 2007 to December 2012, 98 patients treated with NACT were identified and matched to 98 PDS patients. Demographic, clinicopathologic, and other variables are listed in Table 1. The rate of optimal cytoreduction was 87.8% and 51% in the NACT and PDS groups, respectively (P b 0.0001). Postoperative complications affected 34% of patients in the NACT group and 68% of patients in the PDS group (P b 0.0001). Time to recurrence was 16 months in both groups (P = 1). Conclusions: The use of NACT in the treatment of EOC does not affect the time to recurrence but does increase the rate of optimal cytoreductive surgery and decrease the number of postoperative complications. This indicates that the use of NACT does not adversely
118
Abstracts / Gynecologic Oncology 137 (2015) 92–179
affect time to recurrence but may decrease the perioperative morbidity associated with cytoreductive surgery.
Table 1 Demographic, clinicopathologic, and outcome data.
Age BMI Race White Black Other Unknown Primary site Ovarian Fallopian tube Primary peritoneal Unknown Histology Serous Endometrioid Mucinous Clear cell Other Debulking status Suboptimal N1 cm Optimal 0.5 cm–1 cm Optimal b 0.5 cm Optimal, microscopic Stage II III IV Missing Postoperative complication Time to recurrence
NACT
PDS
64.5 28.5 84 4 3 8
63.4 28 84 7 0 7
67 21 7 3
60 31 7 0
80 3 1 1 8
85 0 0 4 9
5 7 22 64
27 21 18 32
N/A
0 81 11 6
68% 16 months
34% 16 months
Neoadjuvant chemotherapy (NACT), primary debulking surgery (PDS).
doi:10.1016/j.ygyno.2015.01.292
290 - Poster Session Time to chemotherapy following surgical cytoreduction for epithelial ovarian cancer: Does neoadjuvant chemotherapy make a difference? M.M. Boisen, J. Berger, J. Phillips, S.E. Taylor, A. Peters, J.T. Comerci, R.P. Edwards, J.L. Kelley III, P. Sukumvanich, M. Huang. Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA Objectives: Neoadjuvant chemotherapy (NACT) prior to surgical cytoreduction for advanced epithelial ovarian cancer (EOC) is thought to have equivalent patient outcomes when compared to primary debulking (PDS). The NACT approach may reduce the need for morbid surgical procedures, shorten hospital stays, and shorten the interval to adjuvant therapy. We sought to determine whether NACT affects time to adjuvant chemotherapy following surgical cytoreduction. Methods: Institutional review board approval was obtained. Patients who underwent primary treatment for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers at our institution from January, 2007 to December, 2013 were included. NACT followed by cytoreduction and PDS cases were matched 1:1. Patient charts were abstracted for demographic information, treatment characteristics, and patient outcomes. Statistical tests were performed with Fisher's exact test and the Mann–Whitney test with P b 0.05 considered significant. Results: A total of 196 patients were identified, 98 in the NACT and PDS arms, respectively. Mean age in the NACT arm was 63.4 years and was 64.5 years in the PDS arm. There were 60 ovarian, 31
fallopian tube, and 7 primary peritoneal cancers in the PDS arm and 61 ovarian, 21 fallopian tube, and 7 primary peritoneal cancers in the NACT arm. The majority of patients (165 [84%]) had serous tumors. In the NACT arm, the median number of chemotherapy cycles prior to cytoreduction was 4 (range, 1–7). Seventy-one (72%) and 93 (95%) patients were optimally cytoreduced in the PDS and NAC groups, respectively. Thirty-three (34%) patients in the NACT arm had surgical complications as compared to 67 (68%) in the PDS group (P b 0.0001). Median time to initiation of adjuvant chemotherapy following cytoreduction in the NACT group was 34.0 days compared to 36.0 days in the PDS group. These differences were not statistically significant (P = 0.73). Conclusions: Time to initiation of chemotherapy did not differ between the two groups, despite fewer surgical complications in the NACT arm. Further work to assess how time to adjuvant chemotherapy affects overall outcomes is warranted.
doi:10.1016/j.ygyno.2015.01.293
291 - Poster Session Visceral adiposity associated with increased risk of death from ovarian cancer Y. Zhang, P. Allen, L.A. Meyer, C.C.L. Sun, K.M. Basen-Engquist, K.H. Lu, A.H. Klopp. The University of Texas MD Anderson Cancer Center, Houston, TX, USA Objectives: Central, or visceral, obesity increases the risk of developing ovarian cancer. The impact of visceral obesity on recurrence in women with ovarian cancer is unknown. We hypothesized that excess visceral adipose may increase the risk of recurrence in patients with ovarian cancer. Methods: The medical records of 185 patients with stage I–IV ovarian cancer who underwent initial surgery between January 1, 2001 and December 31, 2009 on a tumor banking protocol at our institution were reviewed. The thickness of perirenal adipose tissue, an established surrogate measure of visceral adiposity, was measured on computed tomography scans obtained within 6 months of initial diagnosis. Disease-free survival (DFS) and overall survival (OS) were computed using the Kaplan–Meier method and log-rank tests. Univariate and multivariate Cox proportional hazards' analyses were used to determine relationships between clinical variables and DFS and OS. Results: Patients with greater than the median thickness of perirenal adipose tissue (5 mm) had lower rates of DFS at 5 years (45.6% vs. 53.8%, P = 0.05). On univariate analysis, stage III or IV disease, treatment with neoadjuvant chemotherapy, elevated posttreatment CA-125, and N2 cm of residual disease was associated with lower DFS. Elevated body mass index was not associated with DFS. In multivariate analysis, N5 mm of perirenal adipose tissue was associated with a higher risk of death from ovarian cancer (HR = 1.37, 95% CI 1.03–1.82). Stage, residual disease, and treatment with neoadjuvant chemotherapy also remained associated with a lower DFS on multivariate analysis. Greater than 5 mm of perirenal adipose tissue was also independently predictive of a higher risk of death on multivariate analysis (HR = 1.46, 95% CI 1.08–1.98). Conclusions: Our data suggest that increased visceral adipose, but not body mass index, is associated with a higher risk of death from ovarian cancer. Strategies targeted at reducing visceral adipose tissue may improve outcomes in women who have been diagnosed with ovarian cancer.
doi:10.1016/j.ygyno.2015.01.294