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Lee, Paula Sowon

Positions:

Assistant Professor of Obstetrics and Gynecology

Obstetrics and Gynecology, Gynecologic Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2000

M.D. — Tulane University

Residency, Ob/Gyn

Duke University

Grants:

PP LNM 01 FILM

Administered By
Duke Cancer Institute
AwardedBy
Novadaq Technologies Inc.
Role
Principal Investigator
Start Date
April 01, 2016
End Date
March 31, 2021

A Pilot Study on H.O.P.E: Helping Ovarian Cancer Patients Cope with Disease Recurrence

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
Foundation for Women's Cancer
Role
Principal Investigator
Start Date
April 01, 2014
End Date
March 31, 2016

Publications:

Performance of sentinel lymph node biopsy in high-risk endometrial cancer.

To determine the rate and performance of sentinel lymph node (SLN) mapping among women with high-risk endometrial cancers.Patients diagnosed between 2012 and 2015 with uterine cancer of grade 3 endometrioid, clear cell, serous or carcinosarcoma histology and who underwent SLN mapping prior to full pelvic lymph node dissection were included. Subjects underwent methylene blue or ICG injection for laparoscopic (N = 16) or robotic-assisted laparoscopic (N = 20) staging. Outcomes included SLN mapping rates, SLN and non-SLN positive rates, false negative SLN algorithm rate, and the negative predictive value (NPV) of the SLN algorithm. Fisher's exact test was used to compare mapping and node positivity rates.9/36 (25%) patients with high-risk uterine cancer had at least one metastatic lymph node identified. Successful mapping occurred in 30/36 (83%) patients. SLN mapped to pelvic nodes bilaterally in 20 (56%), unilaterally in 9 (25%), and aortic nodes only in 1 (3%). Malignancy was identified in 14/95 (15%) of all sentinel nodes and 12/775 (1.5%) of all non-sentinel nodes (p < 0.001). The false negative rate of SLN mapping alone was 2/26 (7.7%); the NPV was 92.3%. When the SLN algorithm was applied retrospectively the false negative rate was 0/31 (0%); the NPV was 100%.SLN mapping rates for high-risk cancers are slightly lower than in prior reports of lower risk cancers. The NPV of the SLN mapping alone is 92% and rises to 100% when the SLN algorithm is applied. Such results are acceptable and consistent with larger subsets of lower risk endometrial cancers.

Authors
Ehrisman, J; Secord, AA; Berchuck, A; Lee, PS; Di Santo, N; Lopez-Acevedo, M; Broadwater, G; Valea, FA; Havrilesky, LJ
MLA Citation
Ehrisman, J, Secord, AA, Berchuck, A, Lee, PS, Di Santo, N, Lopez-Acevedo, M, Broadwater, G, Valea, FA, and Havrilesky, LJ. "Performance of sentinel lymph node biopsy in high-risk endometrial cancer." Gynecologic oncology reports 17 (August 2016): 69-71.
PMID
27453926
Source
epmc
Published In
Gynecologic Oncology Reports
Volume
17
Publish Date
2016
Start Page
69
End Page
71
DOI
10.1016/j.gore.2016.04.002

Conservative management of morbidly adherent placenta: expert review.

Over the last century, the incidence of placenta accreta, increta, and percreta, collectively referred to as morbidly adherent placenta, has risen dramatically. Planned cesarean hysterectomy at the time of cesarean delivery is the standard recommended treatment in the United States. Recently, interest in conservative management has resurged, especially in Europe. The aims of this review are the following: (1) to provide an overview of methods used for conservative management, (2) to discuss clinical implications for both clinicians and patients, and (3) to identify areas in need of further research.

Authors
Fox, KA; Shamshirsaz, AA; Carusi, D; Secord, AA; Lee, P; Turan, OM; Huls, C; Abuhamad, A; Simhan, H; Barton, J; Wright, J; Silver, R; Belfort, MA
MLA Citation
Fox, KA, Shamshirsaz, AA, Carusi, D, Secord, AA, Lee, P, Turan, OM, Huls, C, Abuhamad, A, Simhan, H, Barton, J, Wright, J, Silver, R, and Belfort, MA. "Conservative management of morbidly adherent placenta: expert review." American journal of obstetrics and gynecology 213.6 (December 2015): 755-760. (Review)
PMID
25935779
Source
epmc
Published In
American Journal of Obstetrics & Gynecology
Volume
213
Issue
6
Publish Date
2015
Start Page
755
End Page
760
DOI
10.1016/j.ajog.2015.04.034

Improving Quality and Decreasing Cost in Gynecologic Oncology Care. Society of Gynecologic Oncology Recommendations for Clinical Practice

Authors
Rimel, BJ; Burke, WM; Higgins, RV; Lee, PS; Lutman, CV; Parker, L
MLA Citation
Rimel, BJ, Burke, WM, Higgins, RV, Lee, PS, Lutman, CV, and Parker, L. "Improving Quality and Decreasing Cost in Gynecologic Oncology Care. Society of Gynecologic Oncology Recommendations for Clinical Practice." Obstetrical & Gynecological Survey 70.9 (September 2015): 570-571.
Source
crossref
Published In
Obstetrical and Gynecological Survey
Volume
70
Issue
9
Publish Date
2015
Start Page
570
End Page
571
DOI
10.1097/01.ogx.0000470820.38134.12

Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, open-label, two-group, two-stage, phase 2 study.

BACKGROUND: Activating FGFR2 mutations are found in 10-16% of primary endometrial cancers and provide an opportunity for targeted therapy. We assessed the safety and activity of dovitinib, a potent tyrosine-kinase inhibitor of fibroblast growth factor receptors, VEGF receptors, PDGFR-β, and c-KIT, as second-line therapy both in patients with FGFR2-mutated (FGFR2(mut)) endometrial cancer and in those with FGFR2-non-mutated (FGFR2(non-mut)) endometrial cancer. METHODS: In this phase 2, non-randomised, two-group, two-stage study, we enrolled adult women who had progressive disease after first-line chemotherapy for advanced or metastatic endometrial cancer from 46 clinical sites in seven countries. We grouped women according to FGFR2 mutation status and gave all women dovitinib (500 mg per day, orally, on a 5-days-on and 2-days-off schedule) until disease progression, unacceptable toxicity, death, or study discontinuation for any other reason. The primary endpoint was proportion of patients in each group who were progression-free at 18 weeks. For each group, the second stage of the trial (enrolment of 20 additional patients) could proceed if at least eight of the first 20 treated patients were progression free at 18 weeks. Activity was assessed in all enrolled patients and safety was assessed in all patients who received at least one dose of dovitinib. The completed study is registered with ClinicalTrials.gov, number NCT01379534. FINDINGS: Of 248 patients with FGFR2 prescreening results, 27 (11%) had FGFR2(mut) endometrial cancer. Between Feb 17, 2012, and Dec 13, 2013, we enrolled 22 patients in the FGFR2(mut) group and 31 patients in the FGFR2(non-mut) group. Seven (31·8%, 95% CI 13·9-54·9) patients in the FGFR2(mut) group and nine (29·0%, 14·2-48·0) in the FGFR2(non-mut) group were progression-free at 18 weeks. On the basis of predefined criteria, neither group continued to stage two: seven (35%) of the first 20 patients in the FGFR2(mut) group were progression free at 18 weeks, as were five (25%) of the first 20 in the FGFR2(mut) population. Rates of treatment-emergent adverse events were similar between groups and events were most frequently gastrointestinal. Overall, the most common grade 3 or 4 adverse events suspected to be related to the study drug were hypertension (nine patients; 17%) and diarrhoea (five; 9%). The most frequently reported serious adverse events suspected to be related to study drug were pulmonary embolism (four patients; 8%), vomiting (four; 8%), dehydration (three; 6%), and diarrhoea (three; 6%). Only one death was deemed to be treatment-related: one patient in the FGFR2(non-mut) group died from cardiac arrest with contributing reason of pulmonary embolism (grade 4, suspected to be study drug related) 4 days previously. INTERPRETATION: Second-line dovitinib in FGFR2(mut) and FGFR2(non-mut) advanced or metastatic endometrial cancer had single-agent activity, although it did not reach the prespecified study criteria. Observed treatment effects seemed independent of FGFR2 mutation status. These data should be considered exploratory and additional studies are needed. FUNDING: Novartis Pharmaceuticals.

Authors
Konecny, GE; Finkler, N; Garcia, AA; Lorusso, D; Lee, PS; Rocconi, RP; Fong, PC; Squires, M; Mishra, K; Upalawanna, A; Wang, Y; Kristeleit, R
MLA Citation
Konecny, GE, Finkler, N, Garcia, AA, Lorusso, D, Lee, PS, Rocconi, RP, Fong, PC, Squires, M, Mishra, K, Upalawanna, A, Wang, Y, and Kristeleit, R. "Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, open-label, two-group, two-stage, phase 2 study." The Lancet. Oncology 16.6 (June 2015): 686-694.
PMID
25981814
Source
epmc
Published In
The Lancet Oncology
Volume
16
Issue
6
Publish Date
2015
Start Page
686
End Page
694
DOI
10.1016/s1470-2045(15)70159-2

Comprehensive care in gynecologic oncology: The importance of palliative care.

Authors
Landrum, LM; Blank, S; Chen, L-M; Duska, L; Bae-Jump, V; Lee, PS; Levine, L; McCourt, C; Moore, KN; Urban, RR
MLA Citation
Landrum, LM, Blank, S, Chen, L-M, Duska, L, Bae-Jump, V, Lee, PS, Levine, L, McCourt, C, Moore, KN, and Urban, RR. "Comprehensive care in gynecologic oncology: The importance of palliative care." Gynecologic oncology 137.2 (May 2015): 193-202.
PMID
25749723
Source
epmc
Published In
Gynecologic Oncology
Volume
137
Issue
2
Publish Date
2015
Start Page
193
End Page
202
DOI
10.1016/j.ygyno.2015.02.026

Improving quality and decreasing cost in gynecologic oncology care. Society of gynecologic oncology recommendations for clinical practice.

OBJECTIVE: To identify potential cost savings in gynecologic oncology care without sacrificing quality. METHODS: Members of the Clinical Practice Committee of the Society of Gynecologic Oncology were asked to review current practice patterns in gynecologic oncology and assess the potential for cost savings founded on evidence-based medicine and current guidelines. RESULTS: Five clinical practices were identified including the following: vaginal cytology for endometrial cancer survivors; colposcopy for low grade cytologic abnormalities for cervical cancer survivors; routine imaging studies for gynecologic cancer survivors; screening for ovarian cancer with serum biomarkers and ultrasound; and improving palliative care for gynecologic cancer patients. Review of the published literature and guidelines were performed to make evidence-based recommendations for cost effective quality gynecologic oncology care. RECOMMENDATIONS: • Do not perform Pap tests of the vaginal cuff in patients with a history of endometrial cancer. • Do not perform colposcopy for low grade Pap tests in women with a history of cervical cancer. • Avoid routine imaging for cancer surveillance in asymptomatic women with gynecologic cancer, specifically ovarian, endometrial, cervical, vulvar and vaginal cancer. • Do not screen women at low risk for ovarian cancer with ultrasound or CA-125 or other biomarkers. • Do not delay basic level palliative care for women with advanced or relapsed gynecologic cancer, do refer to a palliative care specialist when needed, and avoid unnecessary treatments at life's end.

Authors
Rimel, BJ; Burke, WM; Higgins, RV; Lee, PS; Lutman, CV; Parker, L
MLA Citation
Rimel, BJ, Burke, WM, Higgins, RV, Lee, PS, Lutman, CV, and Parker, L. "Improving quality and decreasing cost in gynecologic oncology care. Society of gynecologic oncology recommendations for clinical practice." Gynecologic oncology 137.2 (May 2015): 280-284.
PMID
25735256
Source
epmc
Published In
Gynecologic Oncology
Volume
137
Issue
2
Publish Date
2015
Start Page
280
End Page
284
DOI
10.1016/j.ygyno.2015.02.021

Vaginal cuff thermal injury by mode of colpotomy at total laparoscopic hysterectomy: a randomized clinical trial.

STUDY OBJECTIVE: To evaluate if the use of Valleylab mode ("V mode") (Covidien, Mansfield, MA) electrothermal energy for colpotomy during total laparoscopic hysterectomy (LH) results in a smaller margin of thermal injury to the upper vagina compared with traditional cut/coagulate (cut/coag) electrothermal energy. DESIGN: Prospective randomized clinical trial (Canadian Task Force classification I). SETTING: University medical center. PATIENTS: A total of 101 subjects who underwent LH between June 2010 and August 2012. INTERVENTIONS: Subjects were randomized to colpotomy by V mode electrothermal energy or cut/coag electrothermal energy. MEASUREMENTS AND MAIN RESULTS: The primary end point was the median depth of thermal injury measured in millimeters. The secondary end points included the proportion of subjects who developed granulation tissue, induration, infection, or dehiscence at the vaginal cuff at 4 weeks, 3 months, or 6 months postoperatively. There was no significant difference in the median depth of thermal injury in the cut/coag and V mode arms (anterior margin: 0.68 mm vs 0.63 mm [p = .94], posterior margin: 0.66 mm vs 0.70 mm [p = .87], respectively). Twenty-seven percent of subjects in each arm developed at least 1 of the clinical end points at 4 weeks, 3 months, or 6 months postoperatively (granulation tissue: 6%-18% vs 8%-21%, induration: 0%-2% vs 4%-5%, infection: 0%-4% vs 0%-10%, dehiscence: 2% vs 0% in the cut/coag and V mode arms, respectively), with no difference between arms (p = 1.0). CONCLUSION: The V mode does not reduce the depth of thermal injury compared with cut/coag electrothermal energy when used for colpotomy incision during total laparoscopic hysterectomy (Clinical Trials.gov ID: NCT02080546).

Authors
Teoh, D; Lowery, WJ; Jiang, X; Ehrisman, J; Halvorson, P; Broadwater, G; Bentley, R; Secord, AA; Sobolewski, C; Berchuck, A; Havrilesky, LJ; Valea, FA; Lee, PS
MLA Citation
Teoh, D, Lowery, WJ, Jiang, X, Ehrisman, J, Halvorson, P, Broadwater, G, Bentley, R, Secord, AA, Sobolewski, C, Berchuck, A, Havrilesky, LJ, Valea, FA, and Lee, PS. "Vaginal cuff thermal injury by mode of colpotomy at total laparoscopic hysterectomy: a randomized clinical trial." February 2015.
PMID
25305572
Source
epmc
Published In
Journal of Minimally Invasive Gynecology
Volume
22
Issue
2
Publish Date
2015
Start Page
227
End Page
233
DOI
10.1016/j.jmig.2014.10.002

Vaginal Cuff Thermal Injury by Mode of Colpotomy at Total Laparoscopic Hysterectomy: A Randomized Clinical Trial

Authors
Teoh, D; Lowery, WJ; Jiang, X; Ehrisman, J; Halvorson, P; Broadwater, G; Bentley, R; Secord, AA; Sobolewski, C; Berchuck, A; Havrilesky, LJ; Valea, FA; Lee, PS
MLA Citation
Teoh, D, Lowery, WJ, Jiang, X, Ehrisman, J, Halvorson, P, Broadwater, G, Bentley, R, Secord, AA, Sobolewski, C, Berchuck, A, Havrilesky, LJ, Valea, FA, and Lee, PS. "Vaginal Cuff Thermal Injury by Mode of Colpotomy at Total Laparoscopic Hysterectomy: A Randomized Clinical Trial." JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY 22.2 (February 2015): 227-233.
Source
wos-lite
Published In
Journal of Minimally Invasive Gynecology
Volume
22
Issue
2
Publish Date
2015
Start Page
227
End Page
233
DOI
10.1016/j.jmig.2014.10.002

Improving quality and decreasing cost in gynecologic oncology care. Society of gynecologic oncology recommendations for clinical practice

© 2015 Elsevier Inc.Objective. To identify potential cost savings in gynecologic oncology care without sacrificing quality. Methods. Members of the Clinical Practice Committee of the Society of Gynecologic Oncology were asked to review current practice patterns in gynecologic oncology and assess the potential for cost savings founded on evidence-based medicine and current guidelines. Results. Five clinical practiceswere identified including the following: vaginal cytology for endometrial cancer survivors; colposcopy for lowgrade cytologic abnormalities for cervical cancer survivors; routine imaging studies for gynecologic cancer survivors; screening for ovarian cancer with serum biomarkers and ultrasound; and improving palliative care for gynecologic cancer patients. Review of the published literature and guidelines were performed tomake evidence-based recommendations for cost effective quality gynecologic oncology care. Recommendations. o Do not perform Pap tests of the vaginal cuff in patients with a history of endometrial cancer. o Do not perform colposcopy for low grade Pap tests in women with a history of cervical cancer. o Avoid routine imaging for cancer surveillance in asymptomatic women with gynecologic cancer, specifically ovarian, endometrial, cervical, vulvar and vaginal cancer. o Do not screen women at low risk for ovarian cancer with ultrasound or CA-125 or other biomarkers. o Do not delay basic level palliative care for women with advanced or relapsed gynecologic cancer, do refer to a palliative care specialist when needed, and avoid unnecessary treatments at life's end.

Authors
Rimel, BJ; Burke, WM; Higgins, RV; Lee, PS; Lutman, CV; Parker, L
MLA Citation
Rimel, BJ, Burke, WM, Higgins, RV, Lee, PS, Lutman, CV, and Parker, L. "Improving quality and decreasing cost in gynecologic oncology care. Society of gynecologic oncology recommendations for clinical practice." Gynecologic Oncology 137.2 (January 1, 2015): 280-284.
Source
scopus
Published In
Gynecologic Oncology
Volume
137
Issue
2
Publish Date
2015
Start Page
280
End Page
284
DOI
10.1016/j.ygyno.2015.02.021

Comprehensive care in gynecologic oncology: The importance of palliative care

Authors
Landrum, LM; Blank, S; Chen, LM; Duska, L; Bae-Jump, V; Lee, PS; Levine, L; McCourt, C; Moore, KN; Urban, RR
MLA Citation
Landrum, LM, Blank, S, Chen, LM, Duska, L, Bae-Jump, V, Lee, PS, Levine, L, McCourt, C, Moore, KN, and Urban, RR. "Comprehensive care in gynecologic oncology: The importance of palliative care." Gynecologic Oncology 137.2 (January 1, 2015): 193-202.
Source
scopus
Published In
Gynecologic Oncology
Volume
137
Issue
2
Publish Date
2015
Start Page
193
End Page
202
DOI
10.1016/j.ygyno.2015.02.026

Patient preferences in advanced or recurrent ovarian cancer.

The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen.Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete-choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed-choice question representing 2 chemotherapy regimens for ovarian cancer.In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P < .0001 for all). The discrete-choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, and 24 months of PFS versus 15 months of PFS were 1.5 (P = .01), 3.4 (P < .001), and 7.5 (P < .001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate.PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment-related toxicity.

Authors
Havrilesky, LJ; Alvarez Secord, A; Ehrisman, JA; Berchuck, A; Valea, FA; Lee, PS; Gaillard, SL; Samsa, GP; Cella, D; Weinfurt, KP; Abernethy, AP; Reed, SD
MLA Citation
Havrilesky, LJ, Alvarez Secord, A, Ehrisman, JA, Berchuck, A, Valea, FA, Lee, PS, Gaillard, SL, Samsa, GP, Cella, D, Weinfurt, KP, Abernethy, AP, and Reed, SD. "Patient preferences in advanced or recurrent ovarian cancer." Cancer 120.23 (December 2014): 3651-3659.
PMID
25091693
Source
epmc
Published In
Cancer
Volume
120
Issue
23
Publish Date
2014
Start Page
3651
End Page
3659
DOI
10.1002/cncr.28940

Corrigendum to: A phase II evaluation of Pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: A Gynecologic Oncology Group Study [Gynecol Oncol 133 (2014) 537–541]

Authors
Campos, SM; Brady, WE; Moxley, KM; O'Cearbhaill, RE; Lee, PS; DiSilvestro, PA; Rotmensch, J; Rose, P; Thaker, PH; O'Malley, DM; ParvizHanjani, ; Zuna, RE; Hensley, ML
MLA Citation
Campos, SM, Brady, WE, Moxley, KM, O'Cearbhaill, RE, Lee, PS, DiSilvestro, PA, Rotmensch, J, Rose, P, Thaker, PH, O'Malley, DM, ParvizHanjani, , Zuna, RE, and Hensley, ML. "Corrigendum to: A phase II evaluation of Pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: A Gynecologic Oncology Group Study [Gynecol Oncol 133 (2014) 537–541]." Gynecologic Oncology 135.3 (December 2014): 624-624.
Source
crossref
Published In
Gynecologic Oncology
Volume
135
Issue
3
Publish Date
2014
Start Page
624
End Page
624
DOI
10.1016/j.ygyno.2014.08.011

A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study

©2014 Published by Elsevier Inc.Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC).Patients and Methods. Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens,measurable disease, and performance status of≤2. Treatment consisted of brivanib 800mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed.Results. Forty-five patients were enrolled. Forty-three patients were eligible and evaluable. Median age was 64 years. Twenty-four patients (55.8%) received prior radiation. Median number of cycles was two (range 1-24). No GI perforations but one rectal fistula were seen. Nine patients had grade 3 hypertension, with one experiencing grade 4 confusion. Eight patients (18.6%; 90% CI 9.6%-31.7%) had responses (one CR and sevenPRs), and 13 patients (30.2%; 90% CI 18.9%-43.9%) were PFS at six months.Median PFS and overall survival (OS) were 3.3 and 10.7 months, respectively. When modeled jointly, VEGF and angiopoietin-2 expression may diametrically predict PFS. Estrogen receptor-α (ER) expression was positively correlated with OS.Conclusion. Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.

Authors
Powell, MA; Sill, MW; Goodfellow, PJ; Benbrook, DM; Lankes, HA; Leslie, KK; Jeske, Y; Mannel, RS; Spillman, MA; Lee, PS; Hoffman, JS; McMeekin, DS; Pollock, PM
MLA Citation
Powell, MA, Sill, MW, Goodfellow, PJ, Benbrook, DM, Lankes, HA, Leslie, KK, Jeske, Y, Mannel, RS, Spillman, MA, Lee, PS, Hoffman, JS, McMeekin, DS, and Pollock, PM. "A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study." Gynecologic Oncology 135.1 (October 1, 2014): 38-43.
Source
scopus
Published In
Gynecologic Oncology
Volume
135
Issue
1
Publish Date
2014
Start Page
38
End Page
43
DOI
10.1016/j.ygyno.2014.07.083

A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study.

Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC).Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and performance status of ≤2. Treatment consisted of brivanib 800 mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed.Forty-five patients were enrolled. Forty-three patients were eligible and evaluable. Median age was 64 years. Twenty-four patients (55.8%) received prior radiation. Median number of cycles was two (range 1-24). No GI perforations but one rectal fistula were seen. Nine patients had grade 3 hypertension, with one experiencing grade 4 confusion. Eight patients (18.6%; 90% CI 9.6%-31.7%) had responses (one CR and seven PRs), and 13 patients (30.2%; 90% CI 18.9%-43.9%) were PFS at six months. Median PFS and overall survival (OS) were 3.3 and 10.7 months, respectively. When modeled jointly, VEGF and angiopoietin-2 expression may diametrically predict PFS. Estrogen receptor-α (ER) expression was positively correlated with OS.Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.

Authors
Powell, MA; Sill, MW; Goodfellow, PJ; Benbrook, DM; Lankes, HA; Leslie, KK; Jeske, Y; Mannel, RS; Spillman, MA; Lee, PS; Hoffman, JS; McMeekin, DS; Pollock, PM
MLA Citation
Powell, MA, Sill, MW, Goodfellow, PJ, Benbrook, DM, Lankes, HA, Leslie, KK, Jeske, Y, Mannel, RS, Spillman, MA, Lee, PS, Hoffman, JS, McMeekin, DS, and Pollock, PM. "A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study." Gynecologic oncology 135.1 (October 2014): 38-43.
PMID
25019571
Source
epmc
Published In
Gynecologic Oncology
Volume
135
Issue
1
Publish Date
2014
Start Page
38
End Page
43
DOI
10.1016/j.ygyno.2014.07.083

A phase II evaluation of pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: a gynecologic oncology group study.

Carcinosarcomas of the female genital tract, also called malignant mixed müllerian tumors, are aggressive biphasic tumors. Second-line treatment options in the recurrent/persistent setting have yielded marginal responses. Given the potential role of angiogenesis in the gynecological carcinomas, pazopanib, a VEGFR inhibitor, was investigated in the management of patients with recurrent carcinosarcoma of the uterus.Eligible patients had histologically confirmed carcinosarcoma of the uterus, a maximum of two prior lines of therapy, adequate renal, hepatic and hematologic function and a performance status of 0-2. Pazopanib was administered orally at 800mg. Two dose reductions were allowed. The primary objective was to ascertain the activity of pazopanib as measured by the proportion of patients who survive progression-free for at least six months and the proportion of patients that have objective tumor responses. Secondary objectives included the frequency and severity of adverse events as assessed by CTCAE v4.0.Of the 22 enrolled patients, 19 were eligible and evaluable for toxicity and survival. No patients had a partial or complete response (90% confidence interval [CI]: 0%, 14.6%). Three patients (15.8%) had PFS ≥6months (90% CI: 4.4%, 35.9%). The median PFS was 2.0months (first and third quartiles were 1.6 and 4.0months, respectively). The median overall survival was 8.7months (first and third quartiles were 2.6 and 14.0months, respectively).Pazopanib demonstrated minimal activity as a second or third line treatment for advanced uterine carcinosarcoma. Potential clinical trial participation should be discussed with the patients.

Authors
Campos, SM; Brady, WE; Moxley, KM; O'Cearbhaill, RE; Lee, PS; DiSilvestro, PA; Rotmensch, J; Rose, PG; Thaker, PH; O'Malley, DM; Hanjani, P; Zuna, RE; Hensley, ML
MLA Citation
Campos, SM, Brady, WE, Moxley, KM, O'Cearbhaill, RE, Lee, PS, DiSilvestro, PA, Rotmensch, J, Rose, PG, Thaker, PH, O'Malley, DM, Hanjani, P, Zuna, RE, and Hensley, ML. "A phase II evaluation of pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: a gynecologic oncology group study." Gynecologic oncology 133.3 (June 2014): 537-541.
PMID
24594074
Source
epmc
Published In
Gynecologic Oncology
Volume
133
Issue
3
Publish Date
2014
Start Page
537
End Page
541
DOI
10.1016/j.ygyno.2014.02.036

Targeting molecular pathways in endometrial cancer: A focus on the FGFR pathway

In the majority of cases, endometrial cancer is localized and highly curable through surgery and adjuvant radiotherapy. However, for patients with advanced or metastatic disease, prognosis is poor. Systemic treatments such as cytotoxic chemotherapy or hormonal therapy can cause significant toxicities including chemotherapy-related gastrointestinal, neurologic, and immunosuppressive toxicities and hormone-related hypertension, increased blood sugar, thrombosis, and pulmonary emboli. In addition, these therapies rarely lead to sustained disease control. Novel therapies with greater efficacy and reduced toxicity are needed. Recent progress in the identification of genetic abnormalities in cell signaling proteins has spurred the development of targeted agents for the treatment of patients with endometrial cancer. The fibroblast growth factor receptor (FGFR) pathway is one of several signaling pathways that have been implicated in the pathogenesis and progression of endometrial cancer. The activity of novel FGFR-targeted agents in preclinical endometrial cancer models and clinical trials will be reviewed. © 2013 Elsevier Ltd.

Authors
Lee, PS; Secord, AA
MLA Citation
Lee, PS, and Secord, AA. "Targeting molecular pathways in endometrial cancer: A focus on the FGFR pathway." Cancer Treatment Reviews 40.4 (May 1, 2014): 507-512. (Review)
Source
scopus
Published In
Cancer Treatment Reviews
Volume
40
Issue
4
Publish Date
2014
Start Page
507
End Page
512
DOI
10.1016/j.ctrv.2013.11.004

Targeting molecular pathways in endometrial cancer: a focus on the FGFR pathway.

In the majority of cases, endometrial cancer is localized and highly curable through surgery and adjuvant radiotherapy. However, for patients with advanced or metastatic disease, prognosis is poor. Systemic treatments such as cytotoxic chemotherapy or hormonal therapy can cause significant toxicities including chemotherapy-related gastrointestinal, neurologic, and immunosuppressive toxicities and hormone-related hypertension, increased blood sugar, thrombosis, and pulmonary emboli. In addition, these therapies rarely lead to sustained disease control. Novel therapies with greater efficacy and reduced toxicity are needed. Recent progress in the identification of genetic abnormalities in cell signaling proteins has spurred the development of targeted agents for the treatment of patients with endometrial cancer. The fibroblast growth factor receptor (FGFR) pathway is one of several signaling pathways that have been implicated in the pathogenesis and progression of endometrial cancer. The activity of novel FGFR-targeted agents in preclinical endometrial cancer models and clinical trials will be reviewed.

Authors
Lee, PS; Secord, AA
MLA Citation
Lee, PS, and Secord, AA. "Targeting molecular pathways in endometrial cancer: a focus on the FGFR pathway." Cancer Treat Rev 40.4 (May 2014): 507-512. (Review)
PMID
24332498
Source
pubmed
Published In
Cancer Treatment Reviews
Volume
40
Issue
4
Publish Date
2014
Start Page
507
End Page
512
DOI
10.1016/j.ctrv.2013.11.004

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients.

The aim of this study is to determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer.We performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hysterectomy (TAH) or minimally invasive hysterectomy (MIH) with use of a disposable uterine manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy at a single academic institution between 2002 and 2012. Exclusion criteria were pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and conversion to laparotomy. Multivariate logistic regression models to determine if type of hysterectomy predicts either LVSI or presence of abnormal cytology were controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal involvement.LVSI was identified in 39/214 (18%) MIH and 44/242 (18%) TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%) TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241 (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a significant predictor of either LVSI (p=0.29) or presence of malignant washings (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03).Minimally invasive hysterectomy with use of a uterine manipulator for endometrial cancer is not associated with LVSI or malignant cytology. Algorithms that better determine the etiology and implications of inconclusive or atypical pelvic cytology are needed to inform the possible additional risk associated with a minimally invasive approach to endometrial cancer.

Authors
Zhang, C; Havrilesky, LJ; Broadwater, G; Di Santo, N; Ehrisman, JA; Lee, PS; Berchuck, A; Alvarez Secord, A; Bean, S; Bentley, RC; Valea, FA
MLA Citation
Zhang, C, Havrilesky, LJ, Broadwater, G, Di Santo, N, Ehrisman, JA, Lee, PS, Berchuck, A, Alvarez Secord, A, Bean, S, Bentley, RC, and Valea, FA. "Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients." Gynecologic oncology 133.2 (May 2014): 211-215.
PMID
24582867
Source
epmc
Published In
Gynecologic Oncology
Volume
133
Issue
2
Publish Date
2014
Start Page
211
End Page
215
DOI
10.1016/j.ygyno.2014.02.025

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: A single institution study of 458 patients

Authors
Zhang, C; Havrilesky, LJ; Broadwater, G; Di Santo, N; Ehrisman, JA; Lee, PS; Berchuck, A; Alvarez Secord, A; Bean, S; Bentley, RC; Valea, FA
MLA Citation
Zhang, C, Havrilesky, LJ, Broadwater, G, Di Santo, N, Ehrisman, JA, Lee, PS, Berchuck, A, Alvarez Secord, A, Bean, S, Bentley, RC, and Valea, FA. "Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: A single institution study of 458 patients." Gynecologic Oncology 133.2 (May 2014): 211-215.
Source
crossref
Published In
Gynecologic Oncology
Volume
133
Issue
2
Publish Date
2014
Start Page
211
End Page
215
DOI
10.1016/j.ygyno.2014.02.025

A phase II evaluation of pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: A Gynecologic Oncology Group study

Objective Carcinosarcomas of the female genital tract, also called malignant mixed müllerian tumors, are aggressive biphasic tumors. Second-line treatment options in the recurrent/persistent setting have yielded marginal responses. Given the potential role of angiogenesis in the gynecological carcinomas, pazopanib, a VEGFR inhibitor, was investigated in the management of patients with recurrent carcinosarcoma of the uterus. Methods Eligible patients had histologically confirmed carcinosarcoma of the uterus, a maximum of two prior lines of therapy, adequate renal, hepatic and hematologic function and a performance status of 0-2. Pazopanib was administered orally at 800 mg. Two dose reductions were allowed. The primary objective was to ascertain the activity of pazopanib as measured by the proportion of patients who survive progression-free for at least six months and the proportion of patients that have objective tumor responses. Secondary objectives included the frequency and severity of adverse events as assessed by CTCAE v4.0. Results Of the 22 enrolled patients, 19 were eligible and evaluable for toxicity and survival. No patients had a partial or complete response (90% confidence interval [CI]: 0%, 14.6%). Three patients (15.8%) had PFS ≥ 6 months (90% CI: 4.4%, 35.9%). The median PFS was 2.0 months (first and third quartiles were 1.6 and 4.0 months, respectively). The median overall survival was 8.7 months (first and third quartiles were 2.6 and 14.0 months, respectively). Conclusion Pazopanib demonstrated minimal activity as a second or third line treatment for advanced uterine carcinosarcoma. Potential clinical trial participation should be discussed with the patients. © 2014 Elsevier Inc.

Authors
Campos, SM; Brady, WE; Moxley, KM; O'Cearbhaill, RE; Lee, PS; Disilvestro, PA; Rotmensch, J; Rose, PG; Thaker, PH; O'Malley, DM; Hanjani, P; Zuna, RE; Hensley, ML
MLA Citation
Campos, SM, Brady, WE, Moxley, KM, O'Cearbhaill, RE, Lee, PS, Disilvestro, PA, Rotmensch, J, Rose, PG, Thaker, PH, O'Malley, DM, Hanjani, P, Zuna, RE, and Hensley, ML. "A phase II evaluation of pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: A Gynecologic Oncology Group study." Gynecologic Oncology 133.3 (January 1, 2014): 537-541.
Source
scopus
Published In
Gynecologic Oncology
Volume
133
Issue
3
Publish Date
2014
Start Page
537
End Page
541
DOI
10.1016/j.ygyno.2014.02.036

Patient preferences in advanced or recurrent ovarian cancer

© 2014 American Cancer Society.BACKGROUND: The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen.METHODS: Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete-choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed-choice question representing 2 chemotherapy regimens for ovarian cancer.RESULTS: In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P<.0001 for all). The discrete-choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, and 24 months of PFS versus 15 months of PFS were 1.5 (P5.01), 3.4 (P<.001), and 7.5 (P<.001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate.CONCLUSIONS: PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment-related toxicity.

Authors
Havrilesky, LJ; Secord, AA; Ehrisman, JA; Berchuck, A; Valea, FA; Lee, PS; Gaillard, SL; Samsa, GP; Cella, D; Weinfurt, KP; Abernethy, AP; Reed, SD
MLA Citation
Havrilesky, LJ, Secord, AA, Ehrisman, JA, Berchuck, A, Valea, FA, Lee, PS, Gaillard, SL, Samsa, GP, Cella, D, Weinfurt, KP, Abernethy, AP, and Reed, SD. "Patient preferences in advanced or recurrent ovarian cancer." Cancer 120.23 (January 1, 2014): 3651-3659.
Source
scopus
Published In
Cancer
Volume
120
Issue
23
Publish Date
2014
Start Page
3651
End Page
3659
DOI
10.1002/cncr.28940

Targeting molecular pathways in endometrial cancer: A focus on the FGFR pathway

Authors
Lee, PS; Secord, AA
MLA Citation
Lee, PS, and Secord, AA. "Targeting molecular pathways in endometrial cancer: A focus on the FGFR pathway." Cancer Treatment Reviews 40.4 (2014): 507-512.
Source
scopus
Published In
Cancer Treatment Reviews
Volume
40
Issue
4
Publish Date
2014
Start Page
507
End Page
512

Palliative and hospice care in gynecologic cancer: a review.

Despite the increasing availability of palliative care, oncology providers often misunderstand and underutilize these resources. The goals of palliative care are relief of suffering and provision of the best possible quality of life for both the patient and her family, regardless of where she is in the natural history of her disease. Lack of understanding and awareness of the services provided by palliative care physicians underlie barriers to referral. Oncologic providers spend a significant amount of time palliating the symptoms of cancer and its treatment; involvement of specialty palliative care providers can assist in managing the complex patient. Patients with gynecologic malignancies remain an ideal population for palliative care intervention. This review of the literature explores the current state of palliative care in the treatment of gynecologic cancers and its implications for the quality and cost of this treatment.

Authors
Lopez-Acevedo, M; Lowery, WJ; Lowery, AW; Lee, PS; Havrilesky, LJ
MLA Citation
Lopez-Acevedo, M, Lowery, WJ, Lowery, AW, Lee, PS, and Havrilesky, LJ. "Palliative and hospice care in gynecologic cancer: a review." Gynecol Oncol 131.1 (October 2013): 215-221. (Review)
PMID
23774302
Source
pubmed
Published In
Gynecologic Oncology
Volume
131
Issue
1
Publish Date
2013
Start Page
215
End Page
221
DOI
10.1016/j.ygyno.2013.06.012

Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer.

OBJECTIVE: To determine if early palliative care intervention in patients with recurrent, platinum-resistant ovarian cancer is potentially cost saving or cost-effective. METHODS: A decision model with a 6 month time horizon evaluated routine care versus routine care plus early referral to a palliative medicine specialist (EPC) for recurrent platinum-resistant ovarian cancer. Model parameters included rates of inpatient admissions, emergency department (ED) visits, chemotherapy administration, and quality of life (QOL). From published ovarian cancer data, we assumed baseline rates over the final 6 months: hospitalization 70%, chemotherapy 60%, and ED visit 30%. Published data from a randomized trial evaluating EPC in metastatic lung cancer were used to model odds ratios (ORs) for potential reductions in hospitalization (OR 0.69), chemotherapy (OR 0.77), and emergency department care (OR 0.74) and improvement in QOL (OR 1.07). The costs of hospitalization, ED visit, chemotherapy, and EPC were based on published data. Ranges were used for sensitivity analysis. Effectiveness was quantified in quality adjusted life years (QALYs); survival was assumed equivalent between strategies. RESULTS: EPC was associated with a cost savings of $1285 per patient over routine care. In sensitivity analysis incorporating QOL, EPC was either dominant or cost-effective, with an incremental cost-effectiveness ratio (ICER) <$50,000/QALY, unless the cost of outpatient EPC exceeded $2400. Assuming no clinical benefit other than QOL (no change in chemotherapy administration, hospitalizations or ED visits), EPC remained highly cost-effective with ICER $37,440/QALY. CONCLUSION: Early palliative care intervention has the potential to reduce costs associated with end of life care in patients with ovarian cancer.

Authors
Lowery, WJ; Lowery, AW; Barnett, JC; Lopez-Acevedo, M; Lee, PS; Secord, AA; Havrilesky, L
MLA Citation
Lowery, WJ, Lowery, AW, Barnett, JC, Lopez-Acevedo, M, Lee, PS, Secord, AA, and Havrilesky, L. "Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer." Gynecologic oncology 130.3 (September 2013): 426-430.
PMID
23769759
Source
epmc
Published In
Gynecologic Oncology
Volume
130
Issue
3
Publish Date
2013
Start Page
426
End Page
430
DOI
10.1016/j.ygyno.2013.06.011

Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer.

OBJECTIVES: (1) To describe the prevalence, timing and setting of documented end-of-life (EOL) discussions in patients with advanced ovarian cancer; and (2) to assess the impact of timing and setting of documented end-of-life discussions on EOL quality care measures. METHODS: A retrospective study of women who died of ovarian cancer diagnosed between 1999 and 2008 was conducted. The following are the EOL quality measures assessed: chemotherapy in the last 14 days of life, >1 hospitalization in the last 30 days, >1 ER visit in the last 30 days, intensive care unit (ICU) admission in the last 30 days, dying in an acute care setting, admitted to hospice ≤3 days. RESULTS: One hundred seventy-seven (80%) patients had documented end-of-life discussions. Median interval from EOL discussion until death was 29 days. Seventy-eight patients (44%) had EOL discussions as outpatient and 99 (56%) as inpatient. Sixty-four out of 220 (29%) patients' care did not conform to at least one EOL quality measure. An EOL discussion at least 30 days before death was associated with a lower incidence of: chemotherapy in the last 14 days of life (p=0.003), >1 hospitalization in the last 30 days (p<0.001), ICU admission in the last 30 days (p=0.005), dying in acute care setting (p=0.01), admitted to hospice ≤3 days (p=0.02). EOL discussion as outpatient was associated with fewer patients hospitalized >1 in the last 30days of life (p<0.001). CONCLUSIONS: End-of-life care discussions are occurring too late in the disease process. Conformance with EOL quality measures can be achieved with earlier end-of-life care discussions.

Authors
Lopez-Acevedo, M; Havrilesky, LJ; Broadwater, G; Kamal, AH; Abernethy, AP; Berchuck, A; Alvarez Secord, A; Tulsky, JA; Valea, F; Lee, PS
MLA Citation
Lopez-Acevedo, M, Havrilesky, LJ, Broadwater, G, Kamal, AH, Abernethy, AP, Berchuck, A, Alvarez Secord, A, Tulsky, JA, Valea, F, and Lee, PS. "Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer." Gynecol Oncol 130.1 (July 2013): 156-161.
PMID
23587882
Source
pubmed
Published In
Gynecologic Oncology
Volume
130
Issue
1
Publish Date
2013
Start Page
156
End Page
161
DOI
10.1016/j.ygyno.2013.04.010

Palliative and hospice care in gynecologic cancer: A review

Despite the increasing availability of palliative care, oncology providers often misunderstand and underutilize these resources. The goals of palliative care are relief of suffering and provision of the best possible quality of life for both the patient and her family, regardless of where she is in the natural history of her disease. Lack of understanding and awareness of the services provided by palliative care physicians underlie barriers to referral. Oncologic providers spend a significant amount of time palliating the symptoms of cancer and its treatment; involvement of specialty palliative care providers can assist in managing the complex patient. Patients with gynecologic malignancies remain an ideal population for palliative care intervention. This review of the literature explores the current state of palliative care in the treatment of gynecologic cancers and its implications for the quality and cost of this treatment. © 2013 Elsevier Inc. All rights reserved.

Authors
Lopez-Acevedo, M; Lowery, WJ; Lowery, AW; Lee, PS; Havrilesky, LJ
MLA Citation
Lopez-Acevedo, M, Lowery, WJ, Lowery, AW, Lee, PS, and Havrilesky, LJ. "Palliative and hospice care in gynecologic cancer: A review." Gynecologic Oncology 131.1 (2013): 215-221.
Source
scival
Published In
Gynecologic Oncology
Volume
131
Issue
1
Publish Date
2013
Start Page
215
End Page
221
DOI
10.1016/j.ygyno.2013.06.012

Metastatic adenocarcinoma after laparoscopic supracervical hysterectomy with morcellation: A case report

Authors
Turner, T; Secord, AA; Lowery, WJ; Sfakianos, G; Lee, PS
MLA Citation
Turner, T, Secord, AA, Lowery, WJ, Sfakianos, G, and Lee, PS. "Metastatic adenocarcinoma after laparoscopic supracervical hysterectomy with morcellation: A case report." Gynecologic Oncology Case Reports 5 (2013): 19-21.
PMID
24371686
Source
scival
Published In
Gynecologic Oncology Reports
Volume
5
Publish Date
2013
Start Page
19
End Page
21
DOI
10.1016/j.gynor.2013.03.002

Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer

Objectives (1) To describe the prevalence, timing and setting of documented end-of-life (EOL) discussions in patients with advanced ovarian cancer; and (2) to assess the impact of timing and setting of documented end-of-life discussions on EOL quality care measures. Methods A retrospective study of women who died of ovarian cancer diagnosed between 1999 and 2008 was conducted. The following are the EOL quality measures assessed: chemotherapy in the last 14 days of life, > 1 hospitalization in the last 30 days, > 1 ER visit in the last 30 days, intensive care unit (ICU) admission in the last 30 days, dying in an acute care setting, admitted to hospice ≤ 3 days. Results One hundred seventy-seven (80%) patients had documented end-of-life discussions. Median interval from EOL discussion until death was 29 days. Seventy-eight patients (44%) had EOL discussions as outpatient and 99 (56%) as inpatient. Sixty-four out of 220 (29%) patients' care did not conform to at least one EOL quality measure. An EOL discussion at least 30 days before death was associated with a lower incidence of: chemotherapy in the last 14 days of life (p = 0.003), > 1 hospitalization in the last 30 days (p < 0.001), ICU admission in the last 30 days (p = 0.005), dying in acute care setting (p = 0.01), admitted to hospice ≤ 3 days (p = 0.02). EOL discussion as outpatient was associated with fewer patients hospitalized > 1 in the last 30 days of life (p < 0.001). Conclusions End-of-life care discussions are occurring too late in the disease process. Conformance with EOL quality measures can be achieved with earlier end-of-life care discussions. © 2013 Elsevier Inc.

Authors
Lopez-Acevedo, M; Havrilesky, LJ; Broadwater, G; Kamal, AH; Abernethy, AP; Berchuck, A; Secord, AA; Tulsky, JA; Valea, F; Lee, PS
MLA Citation
Lopez-Acevedo, M, Havrilesky, LJ, Broadwater, G, Kamal, AH, Abernethy, AP, Berchuck, A, Secord, AA, Tulsky, JA, Valea, F, and Lee, PS. "Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer." Gynecologic Oncology 130.1 (2013): 156-161.
Source
scival
Published In
Gynecologic Oncology
Volume
130
Issue
1
Publish Date
2013
Start Page
156
End Page
161
DOI
10.1016/j.ygyno.2013.04.010

Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer

Objective To determine if early palliative care intervention in patients with recurrent, platinum-resistant ovarian cancer is potentially cost saving or cost-effective. Methods A decision model with a 6 month time horizon evaluated routine care versus routine care plus early referral to a palliative medicine specialist (EPC) for recurrent platinum-resistant ovarian cancer. Model parameters included rates of inpatient admissions, emergency department (ED) visits, chemotherapy administration, and quality of life (QOL). From published ovarian cancer data, we assumed baseline rates over the final 6 months: hospitalization 70%, chemotherapy 60%, and ED visit 30%. Published data from a randomized trial evaluating EPC in metastatic lung cancer were used to model odds ratios (ORs) for potential reductions in hospitalization (OR 0.69), chemotherapy (OR 0.77), and emergency department care (OR 0.74) and improvement in QOL (OR 1.07). The costs of hospitalization, ED visit, chemotherapy, and EPC were based on published data. Ranges were used for sensitivity analysis. Effectiveness was quantified in quality adjusted life years (QALYs); survival was assumed equivalent between strategies. Results EPC was associated with a cost savings of $1285 per patient over routine care. In sensitivity analysis incorporating QOL, EPC was either dominant or cost-effective, with an incremental cost-effectiveness ratio (ICER) < $50,000/QALY, unless the cost of outpatient EPC exceeded $2400. Assuming no clinical benefit other than QOL (no change in chemotherapy administration, hospitalizations or ED visits), EPC remained highly cost-effective with ICER $37,440/QALY. Conclusion Early palliative care intervention has the potential to reduce costs associated with end of life care in patients with ovarian cancer. © 2013 Elsevier Inc. All rights reserved.

Authors
Lowery, WJ; Lowery, AW; Barnett, JC; Lopez-Acevedo, M; Lee, PS; Secord, AA; Havrilesky, L
MLA Citation
Lowery, WJ, Lowery, AW, Barnett, JC, Lopez-Acevedo, M, Lee, PS, Secord, AA, and Havrilesky, L. "Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer." Gynecologic Oncology 130.3 (2013): 426-430.
Source
scival
Published In
Gynecologic Oncology
Volume
130
Issue
3
Publish Date
2013
Start Page
426
End Page
430
DOI
10.1016/j.ygyno.2013.06.011

A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer.

PURPOSE: We conducted a phase I study of dasatinib, an oral SRC-family tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in the treatment of advanced and recurrent epithelial ovarian cancer. EXPERIMENTAL DESIGN: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included defining toxicity, response rate (RR), pharmacokinetics, and pharmacodynamics. Using a "3+3" design, cohorts of three to six patients received paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) every 3 weeks with escalating doses of dasatinib (100, 120, and 150 mg daily), followed by an eight-patient expansion cohort. RESULTS: Twenty patients were enrolled between June 2007 and December 2009. The median age was 61 years (range: 42-82) with a median of 2 prior regimens (range: 0-6), and 71% had platinum-sensitive disease. There were three to six patients in each cohort, and eight in the expansion cohort. Pharmacokinetics were observed over the first two cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia). Other toxicities in all cycles included neutropenia (95% grade 3-4; 91% in the 150 mg dosing cohort), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 40% [three complete responses, (15%); five partial responses, (25%)],10 patients (50%) had stable disease, and two were not evaluable. The PFS(6-month) actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively. CONCLUSIONS: Due to the high incidence of myelosuppression with subsequent cycles, the recommended phase II dose of dasatinib is 150 mg daily in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity.

Authors
Secord, AA; Teoh, DK; Barry, WT; Yu, M; Broadwater, G; Havrilesky, LJ; Lee, PS; Berchuck, A; Lancaster, J; Wenham, RM
MLA Citation
Secord, AA, Teoh, DK, Barry, WT, Yu, M, Broadwater, G, Havrilesky, LJ, Lee, PS, Berchuck, A, Lancaster, J, and Wenham, RM. "A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer." Clin Cancer Res 18.19 (October 1, 2012): 5489-5498.
PMID
22837181
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
18
Issue
19
Publish Date
2012
Start Page
5489
End Page
5498
DOI
10.1158/1078-0432.CCR-12-0507

The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study.

OBJECTIVES: To elucidate the regulation of MASPIN expression in epithelial ovarian cancer (EOC) and associations with p53 status and MASPIN promoter methylation. METHODS: Seven EOC cell lines and 110 advanced stage EOC specimens were analyzed for MASPIN promoter methylation. The cell lines were treated with 5-azacytidine (5-azaC) and evaluated for MASPIN promoter methylation, protein, and mRNA expression. Wild-type (wt) p53 was transiently transfected into the mutant p53 (m p53) SKOV3 cells which were treated with 5-azaC. Phosphor imager analysis quantified the percent methylation of the MASPIN promoter. RESULTS: Of the 3 MASPIN-low m p53 cell lines 2 had greater than 5% MASPIN methylation whereas only 1 of 4 MASPIN-high wt p53 cell lines had greater than 5% MASPIN methylation. Despite the presence of aberrant MASPIN promoter methylation in SKOV3 cells, wt p53-transfection alone resulted in a 3.3-fold increase in MASPIN mRNA. The combination of 5-azaC and wt p53-transfection produced a 36% reduction in MASPIN promoter methylation and 4.5-fold increase in MASPIN transcription. Among the 110 ovarian cancer specimens analyzed for methylation of the MASPIN promoter, 81.8% were weakly methylated, 14.5% were heavily methylated and 3.6% were fully methylated. There was no relationship between promoter methylation and p53 status or MASPIN protein expression. However, MASPIN protein was 6 times more likely to be detected in cancer specimens that harbor a p53 mutation relative to cancer specimens with a wt p53 gene. CONCLUSION: The regulation of MASPIN is a complex multifactorial process that may be controlled by both p53-dependent and -independent epigenetic mechanisms.

Authors
Alvarez Secord, A; Darcy, KM; Hutson, A; Huang, Z; Lee, PS; Jewell, EL; Havrilesky, LJ; Markman, M; Muggia, F; Murphy, SK
MLA Citation
Alvarez Secord, A, Darcy, KM, Hutson, A, Huang, Z, Lee, PS, Jewell, EL, Havrilesky, LJ, Markman, M, Muggia, F, and Murphy, SK. "The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study." Gynecol Oncol 123.2 (November 2011): 314-319.
PMID
21903246
Source
pubmed
Published In
Gynecologic Oncology
Volume
123
Issue
2
Publish Date
2011
Start Page
314
End Page
319
DOI
10.1016/j.ygyno.2011.08.003

Cost comparison of strategies for the management of venous thromboembolic event risk following laparotomy for ovarian cancer.

OBJECTIVE: To evaluate the costs and effectiveness of thromboprophylaxis strategies following laparotomy for ovarian cancer. METHODS: We constructed a decision model to evaluate six strategies for management of postoperative venous thromboembolism (VTE) risk: (1) no thromboprophylaxis; (2) inpatient sequential compression device (SCD); (3) inpatient unfractionated heparin (UFH) 5000 units TID; (4) inpatient low molecular weight heparin (LMWH) 40 mg daily; (5) UFH 5000 units TID×1 month; (6) LMWH 40 mg daily×1 month. Rates of VTE, heparin-induced thrombocytopenia, and significant bleeding for each strategy were obtained from published literature. Costs were based on institutional charges or obtained from the Agency for Healthcare Research and Quality Nationwide Inpatient Sample database for 2008 and average wholesale pricing. Sensitivity analyses were performed to account for uncertainty in estimates. RESULTS: In the base case, UFH×1 month was the least expensive (mean cost $1611) and most effective (VTE risk 1.9%) strategy. LMWH×1 month was equally effective but more expensive ($2197). Inpatient UFH, inpatient LMWH, and SCDs were less effective and more expensive than UFH×1 month. In the sensitivity analysis, cost rankings remained unchanged unless the baseline probability of VTE was assumed <6.5%, the cost of VTE treatment was <$20,000, or the cost of bleeding was >$4500. LMWH×1 month became least expensive when cost was decreased 38%. CONCLUSION: Based on current evidence, extended prophylaxis with UFH is the least expensive and most effective strategy to prevent postoperative VTE following laparotomy for ovarian cancer.

Authors
Teoh, D; Berchuck, A; Alvarez Secord, A; Lee, PS; Lowery, WJ; Sfakianos, GP; Valea, FA; Myers, ER; Havrilesky, LJ
MLA Citation
Teoh, D, Berchuck, A, Alvarez Secord, A, Lee, PS, Lowery, WJ, Sfakianos, GP, Valea, FA, Myers, ER, and Havrilesky, LJ. "Cost comparison of strategies for the management of venous thromboembolic event risk following laparotomy for ovarian cancer." Gynecol Oncol 122.3 (September 2011): 467-472.
PMID
21752434
Source
pubmed
Published In
Gynecologic Oncology
Volume
122
Issue
3
Publish Date
2011
Start Page
467
End Page
472
DOI
10.1016/j.ygyno.2011.06.014

Adverse events associated with laparoscopy vs laparotomy in the treatment of endometrial cancer.

OBJECTIVE: The objective of the study was to compare adverse event rates between laparoscopic vs open surgery for endometrial cancer. STUDY DESIGN: This was a retrospective cohort study comparing 107 women who underwent laparoscopy with 269 age- and body mass index-matched women who underwent laparotomy for treatment of endometrial cancer. RESULTS: Adverse event rates were similar between cohorts (37% laparoscopy vs 43% laparotomy, P=.248). Laparotomies had higher rates of cellulitis (16% vs 7%, P=.018) and open wound infection (9% vs 2%, P=.02), whereas laparoscopy had higher rates of sensory peripheral nerve deficit (5% vs 0%, P=.008) and lymphedema (7% vs 1%, P=.003). Laparoscopy was associated with longer mean operating room times but with shorter hospital stays and lower mean blood loss. CONCLUSION: Laparoscopy was associated with decreased rates of surgical site infections but had an increased risk of peripheral sensory nerve deficits and lymphedema when compared with laparotomy.

Authors
Barnett, JC; Havrilesky, LJ; Bondurant, AE; Fleming, ND; Lee, PS; Secord, AA; Berchuck, A; Valea, FA
MLA Citation
Barnett, JC, Havrilesky, LJ, Bondurant, AE, Fleming, ND, Lee, PS, Secord, AA, Berchuck, A, and Valea, FA. "Adverse events associated with laparoscopy vs laparotomy in the treatment of endometrial cancer." Am J Obstet Gynecol 205.2 (August 2011): 143.e1-143.e6.
PMID
21514921
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
205
Issue
2
Publish Date
2011
Start Page
143.e1
End Page
143.e6
DOI
10.1016/j.ajog.2011.03.012

Expression signatures of TP53 mutations in serous ovarian cancers.

BACKGROUND: Mutations in the TP53 gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease. METHODS: The TP53 coding region was sequenced in 89 frozen serous ovarian cancers, 40 early stage (I/II) and 49 advanced stage (III/IV). Affymetrix U133A expression data was used to define gene expression patterns by mutation, type of mutation, and cancer stage. RESULTS: Missense or chain terminating (null) mutations in TP53 were found in 59/89 (66%) ovarian cancers. Early stage cancers had a significantly higher rate of null mutations than late stage disease (38% vs. 8%, p < 0.03). In advanced stage cases, mutations were more prevalent in short term survivors than long term survivors (81% vs. 30%, p = 0.0004). Gene expression patterns had a robust ability to predict TP53 status within training data. By using early versus late stage disease for out of sample predictions, the signature derived from early stage cancers could accurately (86%) predict mutation status of late stage cancers. CONCLUSIONS: This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.

Authors
Bernardini, MQ; Baba, T; Lee, PS; Barnett, JC; Sfakianos, GP; Secord, AA; Murphy, SK; Iversen, E; Marks, JR; Berchuck, A
MLA Citation
Bernardini, MQ, Baba, T, Lee, PS, Barnett, JC, Sfakianos, GP, Secord, AA, Murphy, SK, Iversen, E, Marks, JR, and Berchuck, A. "Expression signatures of TP53 mutations in serous ovarian cancers. (Published online)" BMC Cancer 10 (May 26, 2010): 237-.
Website
http://hdl.handle.net/10161/4356
PMID
20504346
Source
pubmed
Published In
BMC Cancer
Volume
10
Publish Date
2010
Start Page
237
DOI
10.1186/1471-2407-10-237

Elevated MAL expression is accompanied by promoter hypomethylation and platinum resistance in epithelial ovarian cancer.

We previously found that the gene encoding the Myelin and Lymphocyte protein, MAL, was among the most highly expressed genes in serous ovarian cancers from short-term survivors (<3 years) relative to those of long-term survivors (>7 years). In the present study, we have found that this difference in expression is partially attributable to differences in DNA methylation at a specific region within the MAL promoter CpG island. While MAL was largely unmethylated at the transcription start site (Region 1; -48 to +73 bp) in primary serous ovarian cancers, methylation of an upstream region (Region 2; -452 to -266 bp) was inversely correlated with MAL transcription in the primary cancers (R = -0.463) and ovarian cancer cell lines (R = -0.444). Following treatment of the OVCA432 cell line with 5-azacytidine, methylation of Region 2 decreased from 73.3% to 34.7% (p = 0.007) while Region 1 was unaffected. This was accompanied by a 10-fold increase in MAL expression. Since MAL transcripts are elevated in tumors from short-term survivors, all of whom were treated with platinum-based therapy, MAL may have a role in cisplatin response. We therefore determined the 50% growth inhibitory dose of cisplatin in 30 ovarian cancer cell lines and compared this to MAL expression. MAL transcript levels were higher in the resistant ovarian cell lines (p = 0.04). MAL methylation status may therefore serve as a marker of platinum sensitivity while MAL protein may be a target for development of novel therapies aimed at enhancing sensitivity to platinum-based drugs in ovarian cancer.

Authors
Lee, PS; Teaberry, VS; Bland, AE; Huang, Z; Whitaker, RS; Baba, T; Fujii, S; Secord, AA; Berchuck, A; Murphy, SK
MLA Citation
Lee, PS, Teaberry, VS, Bland, AE, Huang, Z, Whitaker, RS, Baba, T, Fujii, S, Secord, AA, Berchuck, A, and Murphy, SK. "Elevated MAL expression is accompanied by promoter hypomethylation and platinum resistance in epithelial ovarian cancer." International journal of cancer 126.6 (March 2010): 1378-1389.
PMID
19642140
Source
epmc
Published In
International Journal of Cancer
Volume
126
Issue
6
Publish Date
2010
Start Page
1378
End Page
1389
DOI
10.1002/ijc.24797

Association between the N-terminally truncated (DeltaN) p63alpha (DeltaNp63alpha) isoform and debulking status, VEGF expression and progression-free survival in previously untreated, advanced stage epithelial ovarian cancer: A Gynecologic Oncology Group study.

OBJECTIVES: The Gynecologic Oncology Group (GOG) examined the association between the relative expression of the DeltaNp63alpha isoform and clinicopathologic variables, p53 status, angiogenic markers, progression-free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC). METHODS: Immunoblot analysis was used to determine the relative expression of DeltaNp63alpha to beta-actin in lysates of frozen primary tumor from women with previously untreated, advanced stage EOC who participated in a GOG specimen banking protocol and a randomized phase III treatment protocol. RESULTS: DeltaNp63alpha was detected in 49/56 (87.5%) cases with relative expression ranging from 0 to 4.55 (median=0.325). A correlation was observed between the relative expression of DeltaNp63alpha and debulking status (Spearman's correlation coefficient=0.303; p=0.025) and the relative expression of vascular endothelial growth factor (VEGF) (Spearman's correlation coefficient=0.303; p=0.045), but not with p53 status (overexpression or mutation), immunoblot expression of MASPIN, or the relative expression of thrombospondin-1, basic fibroblast growth factor or VEGF receptor-1. A 1.4-fold increase was observed in the risk of disease progression for each unit increase in the relative expression of DeltaNp63alpha using an unadjusted (hazard ratio [HR]=1.459; 95% confidence interval [CI]=1.096-1.942; p=0.010), a full (HR=1.483; 95% CI=1.060-2.076; p=0.021) and a reduced (HR=1.387; 95% CI=1.025-1.877; p=0.034) Cox regression model. The relative expression of DeltaNp63alpha was not associated with OS using an unadjusted, a full or a reduced Cox model. CONCLUSIONS: The relative expression DeltaNp63alpha appears to be associated with debulking status and the relative expression of VEGF and PFS, and to be an independent prognostic factor for disease progression in EOC.

Authors
Jewell, EL; Darcy, KM; Hutson, A; Lee, PS; Havrilesky, LJ; Grace, LA; Berchuck, A; Secord, AA
MLA Citation
Jewell, EL, Darcy, KM, Hutson, A, Lee, PS, Havrilesky, LJ, Grace, LA, Berchuck, A, and Secord, AA. "Association between the N-terminally truncated (DeltaN) p63alpha (DeltaNp63alpha) isoform and debulking status, VEGF expression and progression-free survival in previously untreated, advanced stage epithelial ovarian cancer: A Gynecologic Oncology Group study." Gynecol Oncol 115.3 (December 2009): 424-429.
PMID
19767063
Source
pubmed
Published In
Gynecologic Oncology
Volume
115
Issue
3
Publish Date
2009
Start Page
424
End Page
429
DOI
10.1016/j.ygyno.2009.07.035

Robotic-assisted laparoscopic gynecologic procedures in a fellowship training program.

BACKGROUND AND OBJECTIVE: The robotic surgical platform is an alternative technique to traditional laparoscopy and requires the development of new surgical skills for both the experienced surgeon and trainee. Our goal was to perform an early evaluation of the feasibility of training fellows in robotic-assisted gynecologic procedures at the outset of our incorporation of this technology into clinical practice. METHODS: A systematic approach to fellow training included (1) didactic and hands-on training with the robotic system, (2) instructional videos, (3) assistance at the operating table, and (4) performance of segments of gynecologic procedures in tandem with the attending physician. Time to complete the entire procedure, individual segments, rate of conversion to laparotomy, and complications were recorded. RESULTS: Twenty-one robotic-assisted gynecologic procedures were performed from April 2006 to January 2007. Fellows participated as the console surgeon in 14/21 cases. Thirteen patients (62%) had prior abdominal surgery. Median values with ranges were age 51 years (range, 33 to 90); BMI 28 (range, 19.4 to 43.8); EBL 25 mL (range, 25 to 250); and hospital stay 1 day (range, 1 to 4). No significant difference existed between fellow and attending mean total operative and individual segment times. One conversion to laparotomy was necessary. No major surgical complications occurred. CONCLUSION: These data suggest that it is feasible to incorporate a systematic approach to robotic-assisted laparoscopic training for trainees at the outset of incorporation of this technology into current practice.

Authors
Lee, PS; Bland, A; Valea, FA; Havrilesky, LJ; Berchuck, A; Secord, AA
MLA Citation
Lee, PS, Bland, A, Valea, FA, Havrilesky, LJ, Berchuck, A, and Secord, AA. "Robotic-assisted laparoscopic gynecologic procedures in a fellowship training program." JSLS 13.4 (October 2009): 467-472.
PMID
20202385
Source
pubmed
Published In
JSLS : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons
Volume
13
Issue
4
Publish Date
2009
Start Page
467
End Page
472
DOI
10.4293/108680809X12589998403921

Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy.

Dysregulation of MAL (myelin and lymphocyte protein) has been implicated in several malignancies including esophageal, ovarian, and cervical cancers. The MAL protein functions in apical transport in polarized epithelial cells; therefore, its disruption may lead to loss of organized polarity characteristic of most solid malignancies. Bisulfite sequencing of the MAL promoter CpG island revealed hypermethylation in breast cancer cell lines and 69% of primary tumors analyzed compared with normal breast epithelial cells. Differential methylation between normal and cancer DNA was confined to the proximal promoter region. In a subset of breast cancer cell lines including T47D and MCF7 cells, promoter methylation correlated with transcriptional silencing that was reversible with the methylation inhibitor 5-aza-2'-deoxycytidine. In addition, expression of MAL reduced motility and resulted in a redistribution of lipid raft components in MCF10A cells. MAL protein expression measured by immunohistochemistry revealed no significant correlation with clinicopathologic features. However, in patients who did not receive adjuvant chemotherapy, reduced MAL expression was a significant predictive factor for disease-free survival. These data implicate MAL as a commonly altered gene in breast cancer with implications for response to chemotherapy.

Authors
Horne, HN; Lee, PS; Murphy, SK; Alonso, MA; Olson, JA; Marks, JR
MLA Citation
Horne, HN, Lee, PS, Murphy, SK, Alonso, MA, Olson, JA, and Marks, JR. "Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy." Mol Cancer Res 7.2 (February 2009): 199-209.
PMID
19208741
Source
pubmed
Published In
Molecular cancer research : MCR
Volume
7
Issue
2
Publish Date
2009
Start Page
199
End Page
209
DOI
10.1158/1541-7786.MCR-08-0314

Yin yang 1 modulates taxane response in epithelial ovarian cancer.

Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein, we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary serous epithelial ovarian cancer and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using small interfering RNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in ovarian cancer and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule-stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA cross-linking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1 knockdown in ovarian cancer cell lines results in inhibition of anchorage-independent growth, motility, and proliferation but also increases resistance to taxanes, with no effect on cisplatin sensitivity. These results, together with the prior demonstration of augmentation of microtubule-related genes by E2F3, suggest that enhanced taxane sensitivity in tumors with high YY1/E2F activity may be mediated by modulation of putative target genes with microtubule function.

Authors
Matsumura, N; Huang, Z; Baba, T; Lee, PS; Barnett, JC; Mori, S; Chang, JT; Kuo, W-L; Gusberg, AH; Whitaker, RS; Gray, JW; Fujii, S; Berchuck, A; Murphy, SK
MLA Citation
Matsumura, N, Huang, Z, Baba, T, Lee, PS, Barnett, JC, Mori, S, Chang, JT, Kuo, W-L, Gusberg, AH, Whitaker, RS, Gray, JW, Fujii, S, Berchuck, A, and Murphy, SK. "Yin yang 1 modulates taxane response in epithelial ovarian cancer." Mol Cancer Res 7.2 (February 2009): 210-220.
PMID
19208743
Source
pubmed
Published In
Molecular cancer research : MCR
Volume
7
Issue
2
Publish Date
2009
Start Page
210
End Page
220
DOI
10.1158/1541-7786.MCR-08-0255

Relationship between tamoxifen use and high risk endometrial cancer histologic types.

OBJECTIVES: We wished to determine whether a pre-existing diagnosis of breast cancer or the use of tamoxifen among patients with pre-existing breast cancer influences the histologic type of subsequently diagnosed endometrial carcinoma, the interval between these diagnoses, or survival. METHODS: A single institution retrospective review was performed of all patients who underwent primary surgery for endometrial carcinoma from 1995-2005. We compared the histologic type of endometrial carcinoma among patients with a prior history of breast cancer to those without. Patients with a previous diagnosis of breast cancer were further analyzed by comparing histologic type, progression-free and overall survival between tamoxifen users and non-users. RESULTS: Among 732 women with endometrial carcinoma, 59 patients (8%) had a previous diagnosis of breast cancer, of whom 29 (49%) had used tamoxifen. Women with a history of breast cancer were more likely to have a high risk uterine histologic type (grade 3 endometrioid, papillary serous, or clear cell) (18/59; 31%) than those without this prior malignancy (120/670, 18%; p=0.024). Breast cancer survivors whose endometrial carcinoma was of a high risk histologic type had a longer median duration of prior tamoxifen use compared to those with lower risk histologic types (60 versus 46 months, p=0.034). CONCLUSIONS: Among women with endometrial carcinoma, those with a history of breast cancer are more likely to harbor a high risk uterine histologic subtype. Tamoxifen use of at least 60 months is associated with high risk uterine histologic subtypes when compared to no tamoxifen use. This study adds to existing data suggesting a relationship between tamoxifen use and development of endometrial carcinoma of more aggressive histologic types.

Authors
Bland, AE; Calingaert, B; Secord, AA; Lee, PS; Valea, FA; Berchuck, A; Soper, JT; Havrilesky, L
MLA Citation
Bland, AE, Calingaert, B, Secord, AA, Lee, PS, Valea, FA, Berchuck, A, Soper, JT, and Havrilesky, L. "Relationship between tamoxifen use and high risk endometrial cancer histologic types." Gynecol Oncol 112.1 (January 2009): 150-154.
PMID
18937966
Source
pubmed
Published In
Gynecologic Oncology
Volume
112
Issue
1
Publish Date
2009
Start Page
150
End Page
154
DOI
10.1016/j.ygyno.2008.08.035

Medical and surgical treatment of placenta percreta to optimize bladder preservation.

BACKGROUND: Placenta percreta is associated with significant morbidity and mortality. Interventions are dictated by hemodynamic stability, desire to retain future fertility, and efforts to reduce surgical morbidity at time of delivery. CASES: Two cases of antenatally diagnosed placenta percreta with bladder invasion are presented. Conservative management was used, including endovascular interventions, leaving the placenta in situ, methotrexate, and delayed hysterectomy. Postoperative outcomes were acceptable, with no significant hemorrhagic complications or need for extensive bladder reconstruction. CONCLUSION: Antenatal diagnosis of placenta percreta with bladder invasion is essential in the multidisciplinary management of this potentially catastrophic condition. A comprehensive approach including delayed hysterectomy after medical management resulted in an excellent clinical outcome.

Authors
Lee, PS; Bakelaar, R; Fitpatrick, CB; Ellestad, SC; Havrilesky, LJ; Alvarez Secord, A
MLA Citation
Lee, PS, Bakelaar, R, Fitpatrick, CB, Ellestad, SC, Havrilesky, LJ, and Alvarez Secord, A. "Medical and surgical treatment of placenta percreta to optimize bladder preservation." Obstet Gynecol 112.2 Pt 2 (August 2008): 421-424.
PMID
18669749
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
112
Issue
2 Pt 2
Publish Date
2008
Start Page
421
End Page
424
DOI
10.1097/AOG.0b013e31817e7966

Cyclin E overexpression in epithelial ovarian cancer characterizes an etiologic subgroup.

BACKGROUND: The objective of this study was to determine whether cyclin E overexpression defines an etiologically distinct subgroup of ovarian cancer. METHODS: We analyzed data from 538 epithelial ovarian cancer cases and 629 controls enrolled in a population-based case-control study. Cyclin E protein overexpression was assessed using immunohistochemistry. Case-control and case-case comparisons were done to evaluate the relationship between cyclin E overexpression and epidemiologic risk factors. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) while adjusting for potential confounders. RESULTS: Case-control comparisons showed ovarian cancers with and without cyclin E overexpression have different associations with several epidemiologic risk factors. A dose-response relationship was observed between lifetime ovulatory cycles (LOC) and ovarian cancer that overexpressed cyclin E [OR, 1.8; 95% CI, 1.1-3.0 for moderately high LOC (265-390 cycles) and OR, 2.7; 95% CI, 1.6-4.5 for high LOC (>390 cycles) compared with low LOC (<265 cycles)], but no relationship was seen with cancers that lacked overexpression. The most important components of the LOC variable contributing to the differences in the association with the cyclin E subgroups of ovarian cancer were months of oral contraceptive use and months pregnant. CONCLUSIONS: Cyclin E overexpression is associated with a high number of LOC, largely influenced by oral contraceptive use and pregnancy. This suggests that cyclin E overexpression is a molecular signature characteristic of ovarian cancer cases that may arise via a pathway that involves ovulation-induced alterations.

Authors
Schildkraut, JM; Moorman, PG; Bland, AE; Halabi, S; Calingaert, B; Whitaker, R; Lee, PS; Elkins-Williams, T; Bentley, RC; Marks, JR; Berchuck, A
MLA Citation
Schildkraut, JM, Moorman, PG, Bland, AE, Halabi, S, Calingaert, B, Whitaker, R, Lee, PS, Elkins-Williams, T, Bentley, RC, Marks, JR, and Berchuck, A. "Cyclin E overexpression in epithelial ovarian cancer characterizes an etiologic subgroup." Cancer Epidemiol Biomarkers Prev 17.3 (March 2008): 585-593.
PMID
18349276
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
17
Issue
3
Publish Date
2008
Start Page
585
End Page
593
DOI
10.1158/1055-9965.EPI-07-0596

Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study.

OBJECTIVES: The aim of this study was to explore the co-expression and prognostic relevance of thrombospondin-1 (THBS-1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR-1) in epithelial ovarian cancer (EOC). METHODS: Frozen tumor specimens with defined p53 status were obtained from 67 patients with previously untreated advanced-stage EOC who participated in a Gynecologic Oncology Group specimen-banking protocol and a phase III treatment protocol. Relative expression of the angiogenic markers was quantified by immunoblot analysis and categorized at the median angiogenic marker/actin ratio. p-values are provided as an indication of confidence in the results and to prioritize further testing. RESULTS: An association was observed between categorized VEGF and p53 overexpression (p=0.022), and between VEGFR-1 and race (p=0.027) or histologic subtype (p=0.007). Unadjusted Cox regression analyses indicated that high compared with low THBS-1, but not VEGF or VEGFR-1, was associated with an increased risk of disease progression (hazard ratio [HR]=2.19; 95% confidence interval [CI]=1.29-3.71; p=0.004) and death (HR=1.93; 95% CI=1.12-3.32; p=0.018) whereas bFGF was associated with a reduced risk of disease progression (HR=0.60; 95% CI=0.36-0.99; p=0.046) and death (HR=0.54; 95% CI=0.32-0.93; p=0.026). After adjusting for prognostic factors including clinical characteristics and p53 overexpression, THBS-1 but not bFGF, VEGF or VEGFR-1 was associated with progression-free and overall survival. CONCLUSIONS: These data suggest that high THBS-1 is an independent predictor of worse progression-free and overall survival in women with advanced-stage EOC. A larger prospective study is warranted for validation of these findings.

Authors
Secord, AA; Darcy, KM; Hutson, A; Lee, PS; Havrilesky, LJ; Grace, LA; Berchuck, A; Gynecologic Oncology Group study,
MLA Citation
Secord, AA, Darcy, KM, Hutson, A, Lee, PS, Havrilesky, LJ, Grace, LA, Berchuck, A, and Gynecologic Oncology Group study, . "Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study." Gynecol Oncol 106.1 (July 2007): 221-232.
PMID
17481705
Source
pubmed
Published In
Gynecologic Oncology
Volume
106
Issue
1
Publish Date
2007
Start Page
221
End Page
232
DOI
10.1016/j.ygyno.2007.03.021

Maspin expression in epithelial ovarian cancer and associations with poor prognosis: a Gynecologic Oncology Group study.

OBJECTIVE: This study examined MASPIN expression in human ovarian cancer, and explored the association between MASPIN and prognosis in patients with advanced stage disease treated with first-line cisplatin, carboplatin and/or paclitaxel. METHODS: Frozen primary tumors were obtained from 68 women with previously untreated, advanced stage epithelial ovarian cancer who participated in a specimen banking protocol and a phase III treatment trial conducted by the Gynecologic Oncology Group. Immunoblot analysis was performed in lysates prepared from these tumor specimens to quantify the relative expression of MASPIN/beta-actin. RESULTS: MASPIN was expressed at detected levels in 49 (72%) cases with relative expression ranging from 0.02 to 7.7 (median = 0.2), and was not detected in 19 (28%) of the primary tumors tested. Non-detectable levels of this class II tumor suppressor gene product and inhibitor of angiogenesis were associated with suboptimally-debulked disease (P = 0.034) but not with patient age, FIGO stage, tumor grade, or histologic subtype. After adjusting for prognostic variables for disease progression or death, non-detectable MASPIN expression predicted an increased risk of disease progression (hazard ratio [HR] = 1.89; 95% confidence interval [CI]: 1.04-3.45; P = 0.038) and death (HR = 1.99; 95% CI: 1.07-3.69; P = 0.030). CONCLUSIONS: In advanced stage epithelial ovarian cancer, non-detectable MASPIN appears to be associated with suboptimally-debulked disease and be an independent predictor of an increased risk of progression and death. Further studies are needed to validate these exploratory findings, determine the molecular mechanism controlling MASPIN expression as well as down-regulation and loss in ovarian cancer, and determine if MASPIN can prevent progression of this disease.

Authors
Gynecologic Oncology Group, ; Secord, AA; Lee, PS; Darcy, KM; Havrilesky, LJ; Grace, LA; Marks, JR; Berchuck, A
MLA Citation
Gynecologic Oncology Group, , Secord, AA, Lee, PS, Darcy, KM, Havrilesky, LJ, Grace, LA, Marks, JR, and Berchuck, A. "Maspin expression in epithelial ovarian cancer and associations with poor prognosis: a Gynecologic Oncology Group study." Gynecol Oncol 101.3 (June 2006): 390-397.
PMID
16551475
Source
pubmed
Published In
Gynecologic Oncology
Volume
101
Issue
3
Publish Date
2006
Start Page
390
End Page
397
DOI
10.1016/j.ygyno.2006.02.014

Preoperative evaluation and postoperative management

Authors
Clarke-Pearson, DL; Spillman, MA; Lutman, CV; Lee, PS
MLA Citation
Clarke-Pearson, DL, Spillman, MA, Lutman, CV, and Lee, PS. "Preoperative evaluation and postoperative management." Clinical Gynecology (2006): 233-248.
Source
scival
Published In
Clinical Gynecology
Publish Date
2006
Start Page
233
End Page
248
DOI
10.1016/B978-0-443-06691-7.50022-4

Patterns of gene expression that characterize long-term survival in advanced stage serous ovarian cancers.

PURPOSE: A better understanding of the underlying biology of invasive serous ovarian cancer is critical for the development of early detection strategies and new therapeutics. The objective of this study was to define gene expression patterns associated with favorable survival. EXPERIMENTAL DESIGN: RNA from 65 serous ovarian cancers was analyzed using Affymetrix U133A microarrays. This included 54 stage III/IV cases (30 short-term survivors who lived <3 years and 24 long-term survivors who lived >7 years) and 11 stage I/II cases. Genes were screened on the basis of their level of and variability in expression, leaving 7,821 for use in developing a predictive model for survival. A composite predictive model was developed that combines Bayesian classification tree and multivariate discriminant models. Leave-one-out cross-validation was used to select and evaluate models. RESULTS: Patterns of genes were identified that distinguish short-term and long-term ovarian cancer survivors. The expression model developed for advanced stage disease classified all 11 early-stage ovarian cancers as long-term survivors. The MAL gene, which has been shown to confer resistance to cancer therapy, was most highly overexpressed in short-term survivors (3-fold compared with long-term survivors, and 29-fold compared with early-stage cases). These results suggest that gene expression patterns underlie differences in outcome, and an examination of the genes that provide this discrimination reveals that many are implicated in processes that define the malignant phenotype. CONCLUSIONS: Differences in survival of advanced ovarian cancers are reflected by distinct patterns of gene expression. This biological distinction is further emphasized by the finding that early-stage cancers share expression patterns with the advanced stage long-term survivors, suggesting a shared favorable biology.

Authors
Berchuck, A; Iversen, ES; Lancaster, JM; Pittman, J; Luo, J; Lee, P; Murphy, S; Dressman, HK; Febbo, PG; West, M; Nevins, JR; Marks, JR
MLA Citation
Berchuck, A, Iversen, ES, Lancaster, JM, Pittman, J, Luo, J, Lee, P, Murphy, S, Dressman, HK, Febbo, PG, West, M, Nevins, JR, and Marks, JR. "Patterns of gene expression that characterize long-term survival in advanced stage serous ovarian cancers." Clin Cancer Res 11.10 (May 15, 2005): 3686-3696.
PMID
15897565
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
10
Publish Date
2005
Start Page
3686
End Page
3696
DOI
10.1158/1078-0432.CCR-04-2398
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