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Leigh A Cantrell,
Laura Havrilesky,
Dominic T Moore, David O'Malley,
Margaret Liotta,
Angeles Alvarez Secord,
Christa I Nagel,
David E Cohn,
Amanda Nickles Fader,
Amy H Wallace,
Peter Rose,
Paola A Gehrig
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ABSTRACT: To evaluate the impact of adjuvant post-operative therapy in women with early stage uterine carcinosarcoma.
After IRB approval was obtained at all sites, a multi-center retrospective study of women with FIGO stage I-II uterine carcinosarcoma diagnosed from 1997 to 2007 was conducted. Post-operative treatment included observation (OBS), radiation (RT), chemotherapy (CT) alone or with RT (CT+RT). Data analyzed included demographic and pathologic factors, adjuvant therapy outcomes, and time-to-event information. The Kaplan-Meier method was used to estimate time-to-event functions. Cox regression modeling was used to examine the impact of selected covariates on progression free survival (PFS), and overall survival (OS).
111 women were identified: 94 (85%) had stage I and 17 (15%) had stage II uterine carcinosarcoma. Forty-four women (40%) did not receive adjuvant therapy (OBS), 29 (26%) women had adjuvant CT, 23 (20%) women underwent RT and 15 (14%) women underwent RT+CT. Seventy-three patients were alive without disease and 38 had progressed or died at the close of data collection. In multivariate analysis, CT (p=0.003), LVSI (p<0.0001) and a pre-existing cancer (p=0.004) were most predictive of PFS. LVSI was predictive of shortened OS (p=0.01).
In women with FIGO stage I-II uterine carcinosarcoma, adjuvant chemotherapy is associated with improved PFS compared to radiation or observation alone. Ongoing clinical trials will clarify the role of chemotherapy in women with this disease.
Gynecologic Oncology 06/2012; 127(1):22-6. · 3.89 Impact Factor
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ABSTRACT: To evaluate the efficacy and safety of topotecan in patients with recurrent ovarian, primary peritoneal, and fallopian tube carcinomas.
A randomized phase II analysis of platinum-sensitive patients with measurable disease was performed independently assessing intravenous topotecan 1.25 mg/m2 daily×5 every 21 days (regimen I) and topotecan 4.0 mg/m2/day on days 1, 8, and 15 of a 28-day cycle (regimen II). All patients were treated until disease progression, unmanageable toxicity, or patient refusal. Insufficient accrual related to regimen I resulted in a redesign of the study as a single arm phase II trial assessing only regimen II. More complete efficacy data is presented for regimen II as enrollment on regimen I was insufficient for some analyses.
A total of 81 patients were enrolled. One patient was ineligible. Fifteen patients received regimen I, while 65 patients were treated with regimen II. The response rate on regimen I (daily×5) was 27% (90% CI: 10-51%) and 12% (90% CI: 6-21%) on regimen II (weekly). The median PFS and OS were 4.8 and 27.8 months, respectively, for regimen II. Grade 3/4 neutropenia rate was 93% with daily×5 dosing and 28% for weekly treatment. Febrile neutropenia was very low in both groups.
The weekly regimen of topotecan appeared less active but resulted in less toxicity than the daily regimen in platinum-sensitive recurrent ovarian cancer patients.
Gynecologic Oncology 03/2011; 120(3):454-8. · 3.89 Impact Factor
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ABSTRACT: To determine if the triple negative phenotype (TNP) has prognostic significance in endometrial cancer with respect to various surgicopathologic outcomes and survival.
A tissue microarray was constructed of 396 endometrial cancers from patients who underwent surgical staging at the Ohio State University Medical Center. Immunohistochemistry was used to test for estrogen receptor, progesterone receptor, and HER2 expression. Fluorescent in-situ hybridization (FISH) was also used to test for HER2 amplification. TNP negative patients served as controls. Pearson's chi-square was used to evaluate the association of the TNP with variables associated with a poor prognosis. Cox proportional hazards model was used to perform univariate and multivariate analyses. Progression free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier curves, and the log rank test was used to compare the groups.
Twenty-seven percent of patients had the TNP. The TNP was associated with lymph node metastasis, myometrial invasion (>50%), high grade disease, non-endometrioid histology, and advanced staged disease (p<0.023 for lymph node metastasis and p<0.0001 for all others). The TNP was associated with a significantly worse survival, including a decreased PFS (p=0.009) and OS (p=0.01), but not in a fashion independent of other prognostic variables.
The TNP is associated with advanced stage, high grade, and high risk histology, as well as poor survival. Continued investigation of the exploitation of this phenotype with targeted therapies is necessary.
Gynecologic Oncology 08/2010; 118(2):172-5. · 3.89 Impact Factor
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Amanda Nickles Fader,
Christa Nagel,
Allison E Axtell,
Kristine M Zanotti,
Joseph L Kelley,
Kathleen N Moore,
Angeles Alvarez Secord,
Christine S Walsh,
Warner K Huh,
Paola A Gehrig,
Heidi Gibbons,
Peter G Rose,
Laura J Havrilesky,
Erin Tuller,
Richard D Drake,
Justin Bottsford-Miller, David M O'Malley
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ABSTRACT: To determine recurrence patterns and survival outcomes of stage II uterine papillary serous carcinoma (UPSC) patients treated by various modalities with an emphasis on carboplatin/paclitaxel-based chemotherapy (CT)+/-radiotherapy (RT).
A retrospective, multi-institution study of women with stage II UPSC diagnosed from 1992 to 2006 was performed. All patients underwent comprehensive surgical staging. Treatment included observation (OBS), RT (vaginal brachytherapy, whole pelvic and/or whole abdominal therapy), or >or=3 cycles carboplatin/paclitaxel alone or with RT. Recurrence and survival outcomes were determined.
We identified 55 subjects: 10 treated with OBS, 26 with RT alone and 19 with CT+/-RT. After a median follow-up of 33 mos (range, 10-119), 20 recurrences (36%) were observed. There was an overall difference in recurrence based upon treatment (p=.013). Specifically, all CT+/-RT treated patients had a lower risk of recurrence (11%) compared to patients treated by RT alone (50%) or OBS (50%). No patients treated with both CT+RT (n=12) experienced a recurrence. Treatment with CT was also associated with a decreased risk of recurrence on multivariate analysis (p=.015). Most recurrences were extra-pelvic (70%), occurred within 2 years (85%) and were not salvageable (84%). Five-year progression-free survival was 86% in chemotherapy-treated patients versus 41% in those not receiving chemotherapy (p=.010); overall survival was 88% in chemotherapy-treated patients versus 64% in those not receiving chemotherapy (p=.115).
Stage II UPSC patients have a significant risk for unsalvageable, extra-pelvic recurrence. However, treatment with platinum/taxane therapy+/-RT appears to reduce this risk and is associated with improved progression free survival outcomes.
Gynecologic Oncology 01/2009; 112(3):558-62. · 3.89 Impact Factor
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ABSTRACT: To evaluate the effect of tumor capsule rupture on disease prognosis in stage I epithelial ovarian cancer.
All patients with International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer operated on at the Mayo Clinic and The Ohio State University between January 1991 and December 2007 were identified. Relevant tumor characteristics, procedures performed, adjuvant therapies, and follow-up were recorded and analyzed. Inclusion criteria included comprehensive staging. Cox proportional hazards, Kaplan-Meier estimation, log rank test, and chi test were used for statistical analyses.
There were 161 cases that met inclusion criteria. Seventy-four (46%) patients had intact capsules without positive cytology or surface involvement; 61 (38%) had capsule rupture; 33 (20%) had positive cytology; and 22 (14%) had surface involvement. Overall, 22 of 161 (14%) patients recurred and 12 of 161 (7%) patients died of their disease. In univariable analysis, both intraoperative capsule rupture and positive cytologic washings portended worse disease-free survival (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-8.9; P=.004 and HR 5.2, 95% CI 2.1-12.3; P<.001, respectively) and disease-specific survival (HR 4.1, 95% CI 1.3-15.4; P=.018 and HR 5.9, 95% CI 1.8-19.3; P=.005, respectively). In multivariable analysis, capsule rupture (HR 4.2, 95% CI 1.8-10.9; P=.001) and positive cytologic washings (HR 6.4, 95% CI 2.5-16.0; P<.001) remained independent predictors of worse disease-free survival. Disease-free survival and disease-specific survival were shortest for stage IC cases with positive cytology, surface involvement, or both, that also had intraoperative rupture.
In stage I epithelial ovarian cancer, intraoperative capsule rupture portends a higher risk of disease recurrence and death from disease. Careful intraoperative removal of ovarian masses is important, and recognizing the higher-risk nature of such cases is imperative.
III.
Obstetrics and Gynecology 01/2009; 113(1):11-7. · 4.73 Impact Factor
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ABSTRACT: To estimate the anti-tumor activity and toxicity of paclitaxel poliglumex (PPX) in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal cancer (EOC) in second or third line treatment.
Twenty-five patients received PPX at 235 mg/m(2) every 21 days (Cohort 1). At a planned analysis following first stage accrual, the dose was reduced to 175 mg/m(2) Cohort 2) for additional accrual to 78 patients. RECIST and CTC toxicity criteria were used.
Patients received PPX in the second line (15%) and third line (85%) setting. In cohort 2, 25 out of 47 determined cases (53%) were platinum resistant and 17 out of 43 determined cases (40%) were taxane-resistant. The overall response rates for cohort 2 were 0/49 (0%) CR, 8/49 (16%) PR, and 20/49 (41%) SD. The median progression-free survival (PFS) was 2.8 months (95% CI 1.48-4.8 months) and median overall survival (OS) was 15.4 months. The most frequent grade III or IV toxicities in cohort 2 were: neutropenia (24%/20%), constitutional (8%/0%), gastrointestinal (6%/0%), and neuropathy (24%/0%).
PPX at 175 mg/m(2) every 21 days has a modest activity of limited duration when given as second or third line therapy in patients with epithelial ovarian or primary peritoneal cancer. The incidence of neuropathy using this dose in recurrent ovarian cancer is higher than predicted from studies in other tumors with PPX. The Gynecology Oncology Group (GOG) is currently exploring its use at 135 mg/m(2) every 28 days in a randomized trial evaluating maintenance chemotherapy in first remission.
Gynecologic Oncology 10/2008; 111(3):455-60. · 3.89 Impact Factor
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Robert J Morgan,
Ronald D Alvarez,
Deborah K Armstrong,
Barry Boston,
Lee-may Chen,
Larry Copeland,
Jeff Fowler,
David K Gaffney,
David Gershenson,
Benjamin E Greer, [......],
Carolyn Johnston,
Johnathan M Lancaster,
Shashikant Lele,
Ursula Matulonis, David O'Malley,
Robert F Ozols,
Steven W Remmenga,
Paul Sabbatini,
Julian Schink,
Nelson Teng
Journal of the National Comprehensive Cancer Network: JNCCN 10/2008; 6(8):766-94. · 4.41 Impact Factor
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ABSTRACT: To evaluate VH fibrin sealant's influence on lower extremity lymphedema after inguinal lymphadenectomy in vulvar cancer patients.
Patients undergoing an inguinal lymphadenectomy during the management of vulvar malignancy were randomized to receive sutured closure (SC) vs VH fibrin sealant sprayed into the groin followed by sutured closure (FS). Leg measurements were taken preoperatively and during postoperative encounters when surgical outcomes were assessed. Grade 2 or 3 lymphedema was defined as circumferential measurement increases of 3-5 cm and >5 cm, respectively.
150 patients were enrolled. 137 patients were evaluable for lymphedema analysis with 67 and 70 patients in the SC arm and FS arm, respectively. The incidence of grade 2 and 3 lymphedema was 67%(45/67) in the SC arm, and 60% (42/70) FS arm (p=0.4779). The incidence of lymphedema was strongly associated with inguinal infection (p=0.0165). Lymphedema was not statistically increased in those who received adjuvant radiation. 139 patients remained evaluable for a descriptive analysis of their surgical complications. The overall incidence of complications was 61%(43/70) and 59% (41/69) for SC and FS arms, respectively. There was no statistically significant difference in duration of drains, drain output or incidence of inguinal infections, wound breakdowns or seromas. There was an increased incidence of vulvar infections in the FS arm (23/69) vs (10/70) (p=0.0098). The utilization of a Blake drain was associated with an increase in vulvar (p=0.0157) and inguinal wound breakdown (p=0.0456).
VH fibrin sealant in inguinal lymphadenectomies does not reduce leg lymphedema and may increase the risk for complications in the vulvar wound.
Gynecologic Oncology 07/2008; 110(1):76-82. · 3.89 Impact Factor
