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Patient-derived tumor xenograft model for gynecologic cancer
Abstracts / Gynecologic Oncology 137S1 (2015) 180–209
Methods: A retrospective cohort study was performed of women with endometrial cancer scheduled for robotic surgery from September 2008 to September 2012. Women were divided into three groups based on BMI, and conversion rates to laparotomy were compared. Descriptive and comparative analyses were performed among nonobese, obese, and morbidly obese women who completed robotic surgery. Results: A total of 301 women were scheduled for robotic surgery for endometrial carcinoma, including 88 nonobese (BMI 19–29, μ 25.23), 111 obese (BMI 30–39, μ 34.21), and 102 morbidly obese (BMI 40–71, μ 47.38). Preoperative characteristics were similar except that nonobese patients were slightly older. Conversion to laparotomy occurred in 21 patients (7%), with no difference in conversion rate between BMI categories. Direct comparison between converted and completed robotic patients showed no significant differences in preoperative characteristics, except that obese patients who required conversion had a higher number of previous abdominal surgeries. Reasons for conversion were adhesions (14), metastases (5), large uterine size (1), and difficulty tolerating insufflation (1). Patients completing robotic surgery underwent node dissections at similar rates in all three BMI categories. Operating room time, but not surgical time, was increased in morbidly obese patients. Intraoperative and postoperative complications showed no significant differences between BMI categories. Morbidly obese patients were more likely to have larger uteri and less likely to have grade 3 tumors or vascular space invasion. Pelvic and periaortic lymph node yields were similar across all three categories. Conclusions: Morbid obesity does not increase the rate of conversion to laparotomy or complication rates in patients undergoing robotic surgery for endometrial carcinoma. Node dissections were pathologically equivalent between BMI categories using the robotic platform.
Baseline, perioperative and postoperative characteristics
Preoperative data Average age at surgery Average abdominal surgeries Preoperative grade number 1 2 3 Conversion to laparotomy (n = 21) Average age at surgery Average abdominal surgeries Operative data (robotic cases) LHBSO cases only LHBSO with pelvic nodes LHBSO with pelvic & periaortic nodes Average room time, min Average operative time, min Average EBL Average inpatient stay, days Uterine weight Total sampled pelvic nodes, avg Positive sampled pelvic nodes, avg Total sampled periaortic nodes, avg Positive sampled periaortic nodes % Lymphovascular space invasion Final grade 1 2 3
Nonobese (BMI b30) (n = 88)
Obese Morbidly (BMI 30–40) obese (n = 111) (BMI N40) (n = 102)
P-value
64.79 0.872
63.85 0.85
59.84 0.933
0.004 ns
51 20 10 7(45%)
63 31 13 5(35%)
59 33 4 9(20%)
ns ns ns ns
64.77 0.29
63.94 2.60
59.88 1.56
ns 0.000
11 59 11
6 82 18
15 66 12
ns ns ns
164.98 118.41 114.10 1.16 87.59 21.22 0.04
163.12 119.14 102.38 1.03 103.53 20.35 0.03
182.97 129.60 119.81 1.08 131.50 18.75 0.06
ns ns ns ns ns ns ns
1.46
1.38
1.00
ns
0.00
0.00
0.08
ns
27.16%
28.30%
17.20%
0.000
38 20 17
52 28 20
49 34 4
ns ns 0.002
201
(continued)
Baseline, perioperative and postoperative characteristics
Postoperative data % 30 day readmission % reoperation
Nonobese (BMI b 30) (n = 88)
Obese Morbidly (BMI 30–40) obese (n = 111) (BMI N 40) (n = 102)
P-value
1.23% 0.00%
4.72% 1.89%
ns ns
0.00% 0.00%
doi:10.1016/j.ygyno.2015.01.504
500 — Poster Session Patient-derived tumor xenograft model for gynecologic cancer J.W. Leea, B.G. Kima, T.J. Kima, Y.Y. Leeb, A. Yoonb, W.Y. Kimc, C.H. Choib. aSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, bSamsung Medical Center, Seoul, South Korea, cKangbuk Samsung Hospital, Seoul, South Korea Objectives: A patient-derived tumor xenograft model (PDTX) may provide more accurate and reliable information about individual patients' tumor biology when compared with an established cell line model. This study was designed to study the development of PDTX mice and their genetic and phenotypic stability for gynecologic cancer, including ovarian, endometrial, and cervical cancer. Methods: Small pieces (3 × 3 × 3 mm) of human gynecologic cancer tissue (n = 94) were meticulously grafted under renal capsules of female BALB/C-nude mice within 2 h of surgical removal. Grossly visible tumor tissues serially transplanted for 2–5 generations. After the development of tumor in mice, phenotypic and genetic comparisons were performed between primary tumor and corresponding transplantable xenografts using hematoxylin-and-eosin, Ion Torrent (AmpliSeq Cancer Panel), and array-comparative genomic hybridization (aCGH) analysis. Results: Total tumor tissue engraftment rate was 47.4% (27/57) of ovarian cancer, 46.2% (12/26) of cervical cancer, and 42.9% (6/14) of endometrial cancer. The mean time to the development of first generation in mice was in 5.7 months in ovarian, 5.5 months in cervical, and 4 months in endometrial cancer. Comparison of primary and PDTX tumor tissues showed highly similar histopathologic features. Moreover, analysis of Ion Torrent and aCGH indicated that all examined mutation and genomic alterations found in primary cancer tissues were precisely replicated in the corresponding PDTX tumors. Conclusions: PDTX mice for human gynecologic cancer can be developed as a method of subrenal capsule implantation and have very similar phenotypic and genetic alterations of the original tissues. This has the potential to provide a very effective tool for future personalized therapy and for conducting translational gynecologic cancer research. doi:10.1016/j.ygyno.2015.01.505
501 — Poster Session Evaluation of a novel combination treatment strategy using patient-derived xenografts of uterine carcinosarcoma J. Brouwer-Visser, S. Mi, M. Cossio, M.A. Schwartz, T. Hebert, Y. Zou, D.Y.S. Kuo, G.S. Huang. Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA Objectives: To characterize a newly developed patient-derived xenograft (PDX) model of uterine carcinosarcoma (CS) and to evaluate a novel combination treatment strategy.
Methods: A retrospective cohort study was performed of women with endometrial cancer scheduled for robotic surgery from September 2008 to September 2012. Women were divided into three groups based on BMI, and conversion rates to laparotomy were compared. Descriptive and comparative analyses were performed among nonobese, obese, and morbidly obese women who completed robotic surgery. Results: A total of 301 women were scheduled for robotic surgery for endometrial carcinoma, including 88 nonobese (BMI 19–29, μ 25.23), 111 obese (BMI 30–39, μ 34.21), and 102 morbidly obese (BMI 40–71, μ 47.38). Preoperative characteristics were similar except that nonobese patients were slightly older. Conversion to laparotomy occurred in 21 patients (7%), with no difference in conversion rate between BMI categories. Direct comparison between converted and completed robotic patients showed no significant differences in preoperative characteristics, except that obese patients who required conversion had a higher number of previous abdominal surgeries. Reasons for conversion were adhesions (14), metastases (5), large uterine size (1), and difficulty tolerating insufflation (1). Patients completing robotic surgery underwent node dissections at similar rates in all three BMI categories. Operating room time, but not surgical time, was increased in morbidly obese patients. Intraoperative and postoperative complications showed no significant differences between BMI categories. Morbidly obese patients were more likely to have larger uteri and less likely to have grade 3 tumors or vascular space invasion. Pelvic and periaortic lymph node yields were similar across all three categories. Conclusions: Morbid obesity does not increase the rate of conversion to laparotomy or complication rates in patients undergoing robotic surgery for endometrial carcinoma. Node dissections were pathologically equivalent between BMI categories using the robotic platform.
Baseline, perioperative and postoperative characteristics
Preoperative data Average age at surgery Average abdominal surgeries Preoperative grade number 1 2 3 Conversion to laparotomy (n = 21) Average age at surgery Average abdominal surgeries Operative data (robotic cases) LHBSO cases only LHBSO with pelvic nodes LHBSO with pelvic & periaortic nodes Average room time, min Average operative time, min Average EBL Average inpatient stay, days Uterine weight Total sampled pelvic nodes, avg Positive sampled pelvic nodes, avg Total sampled periaortic nodes, avg Positive sampled periaortic nodes % Lymphovascular space invasion Final grade 1 2 3
Nonobese (BMI b30) (n = 88)
Obese Morbidly (BMI 30–40) obese (n = 111) (BMI N40) (n = 102)
P-value
64.79 0.872
63.85 0.85
59.84 0.933
0.004 ns
51 20 10 7(45%)
63 31 13 5(35%)
59 33 4 9(20%)
ns ns ns ns
64.77 0.29
63.94 2.60
59.88 1.56
ns 0.000
11 59 11
6 82 18
15 66 12
ns ns ns
164.98 118.41 114.10 1.16 87.59 21.22 0.04
163.12 119.14 102.38 1.03 103.53 20.35 0.03
182.97 129.60 119.81 1.08 131.50 18.75 0.06
ns ns ns ns ns ns ns
1.46
1.38
1.00
ns
0.00
0.00
0.08
ns
27.16%
28.30%
17.20%
0.000
38 20 17
52 28 20
49 34 4
ns ns 0.002
201
(continued)
Baseline, perioperative and postoperative characteristics
Postoperative data % 30 day readmission % reoperation
Nonobese (BMI b 30) (n = 88)
Obese Morbidly (BMI 30–40) obese (n = 111) (BMI N 40) (n = 102)
P-value
1.23% 0.00%
4.72% 1.89%
ns ns
0.00% 0.00%
doi:10.1016/j.ygyno.2015.01.504
500 — Poster Session Patient-derived tumor xenograft model for gynecologic cancer J.W. Leea, B.G. Kima, T.J. Kima, Y.Y. Leeb, A. Yoonb, W.Y. Kimc, C.H. Choib. aSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, bSamsung Medical Center, Seoul, South Korea, cKangbuk Samsung Hospital, Seoul, South Korea Objectives: A patient-derived tumor xenograft model (PDTX) may provide more accurate and reliable information about individual patients' tumor biology when compared with an established cell line model. This study was designed to study the development of PDTX mice and their genetic and phenotypic stability for gynecologic cancer, including ovarian, endometrial, and cervical cancer. Methods: Small pieces (3 × 3 × 3 mm) of human gynecologic cancer tissue (n = 94) were meticulously grafted under renal capsules of female BALB/C-nude mice within 2 h of surgical removal. Grossly visible tumor tissues serially transplanted for 2–5 generations. After the development of tumor in mice, phenotypic and genetic comparisons were performed between primary tumor and corresponding transplantable xenografts using hematoxylin-and-eosin, Ion Torrent (AmpliSeq Cancer Panel), and array-comparative genomic hybridization (aCGH) analysis. Results: Total tumor tissue engraftment rate was 47.4% (27/57) of ovarian cancer, 46.2% (12/26) of cervical cancer, and 42.9% (6/14) of endometrial cancer. The mean time to the development of first generation in mice was in 5.7 months in ovarian, 5.5 months in cervical, and 4 months in endometrial cancer. Comparison of primary and PDTX tumor tissues showed highly similar histopathologic features. Moreover, analysis of Ion Torrent and aCGH indicated that all examined mutation and genomic alterations found in primary cancer tissues were precisely replicated in the corresponding PDTX tumors. Conclusions: PDTX mice for human gynecologic cancer can be developed as a method of subrenal capsule implantation and have very similar phenotypic and genetic alterations of the original tissues. This has the potential to provide a very effective tool for future personalized therapy and for conducting translational gynecologic cancer research. doi:10.1016/j.ygyno.2015.01.505
501 — Poster Session Evaluation of a novel combination treatment strategy using patient-derived xenografts of uterine carcinosarcoma J. Brouwer-Visser, S. Mi, M. Cossio, M.A. Schwartz, T. Hebert, Y. Zou, D.Y.S. Kuo, G.S. Huang. Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA Objectives: To characterize a newly developed patient-derived xenograft (PDX) model of uterine carcinosarcoma (CS) and to evaluate a novel combination treatment strategy.