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: ObjectiveTo determine if the type of operative incision influences the adequacy of surgical staging in patients with uterine cancer.: MethodsAll patients with uterine cancer referred to the Swedish Medical Center Cancer Institute for adjuvant radiotherapy between June 1, 1989, and June 1, 1999, who underwent comprehensive surgical staging and for whom complete records could be obtained were eligible. Data on type of incision, weight, medical comorbidities, histology, total number and distribution of lymph nodes (LN), estimated blood loss, complications, and length of stay were abstracted retrospectively. Statistical analysis with two-tailed Student t test, χ2, Fisher’s exact, and Kaplan-Meier survival curves were performed.: ResultsFive hundred four women with uterine cancers were referred to the Cancer Institute with 332 meeting inclusion criteria. A vertical midline incision (ML) was used in 236 (72%) while 96 (28%) received a Pfannenstiel incision (PI). No panniculectomies were performed. There were no statistically significant differences in age, weight, stage, histology, comorbidities, or estimated blood loss between the ML and PI groups. ML was associated with significantly more intraoperative and postoperative complications (34 vs. 7; P = 0.003). When compared to ML a greater number of total LN (21.0 vs. 16.8; P = 0.001) and a comparable number of pelvic LN (13.7 vs. 12.2; P = 0.14) were procured through a PI. More patients with a ML (72% vs. 63%; P = 0.13) had para-aortic lymph nodes (PALN) dissected; however, when obtained equivalent numbers of nodes were removed (3.52 vs. 4.36; P = 0.14). Overall, the median length of stay was statistically shorter for those patients operated on via a PI (4 vs. 3 days; P = 0.007). The projected 5-year disease-free (83% vs. 85%) and disease-specific (87% vs. 85%) survival was unaffected by incision. In the heaviest quartile of patients (>180 lb), a statistically greater number of total LN (23.3 vs. 16.5; P = 0.005) and pelvic LN (16.7 vs. 11.5; P = 0.05) were obtained with a PI. Again, PALN were sampled more frequently (67% vs. 56%; P = 0.45) in patients with a ML, but the mean LN yield was no different (3.91 vs. 5.20; P = 0.37). Likewise, in this heaviest quartile, there were no statically significant differences in operative complications (7 vs. 1; P = 0.43) with either incision.: ConclusionComprehensive surgical staging for uterine cancers can be adequately performed through a PI without greater morbidity or mortality. By using this surgical approach, patients with uterine cancer can benefit from the inherent benefits previously described for PI. Appropriate patient selection, however, is necessary. [Copyright &y& Elsevier]

Objective. Serous ovarian carcinoma (OC) represents a leading cause of cancer-related death among U.S. women. Non-invasive tools have recently emerged for discriminating benign from malignant ovarian masses, but evaluation remains ongoing, without widespread implementation. In the last decade, metabolomics has matured into a new avenue for cancer biomarker development. Here, we sought to identify novel plasma metabolite biomarkers to distinguish serous ovarian carcinoma and benign serous ovarian tumor. Methods. Using liquid chromatography-mass spectrometry, we conducted global and targeted metabolite profiling of plasma isolated at the time of surgery from 50 serous OC cases and 50 serous benign controls. Results. Global lipidomics analysis identified 34metabolites (of 372 assessed) differing significantly (P < 0.05) between cases and controls in both training and testing sets, with 17 candidates satisfying FDR q < 0.05, and two reaching Bonferroni significance. Targeted profiling of ~150 aqueous metabolites identified a single amino acid, alanine, as differentially abundant (P < 0.05). A multivariate classification model built using the top four lipid metabolites achieved an estimated AUC of 0.85 (SD = 0.07) based on Monte Carlo cross validation. Evaluation of a hybrid model incorporating both CA125 and lipid metabolites was suggestive of increased classification accuracy (AUC = 0.91, SD = 0.05) relative to CA125 alone (AUC = 0.87, SD = 0.07), particularly at high fixed levels of sensitivity, without reaching significance. Conclusions. Our results provide insight into metabolic changes potentially correlated with the presence of serous OC versus benign ovarian tumor and suggest that plasma metabolites may help differentiate these two conditions. [ABSTRACT FROM AUTHOR]

Objective We developed and validated a hybrid risk classifier combining serum markers and epidemiologic risk factors to identify post-menopausal women at elevated risk for invasive fallopian tube, primary peritoneal, and ovarian epithelial carcinoma. Methods To select epidemiologic risk factors for use in the classifier, Cox proportional hazards analyses were conducted using 74,786 Women's Health Initiative (WHI) Observational Study (OS) participants. To construct a combination classifier, 210 WHI OS cases and 536 matched controls with serum marker measurements were analyzed; validation employed 143 cases and 725 matched controls from the WHI Clinical Trial (CT) with similar data. Results Analyses identified a combination risk classifier composed of two elevated-risk groups: 1) women with CA125 or HE4 exceeding a 98% specificity threshold; and 2) women with intact fallopian tubes, prior use of menopausal hormone therapy for at least two years, and either a first degree relative with breast or ovarian cancer or a personal history of breast cancer. In the WHI OS population, it classified 13% of women as elevated risk, identifying 30% of ovarian cancers diagnosed up to 7.8 years post-enrollment (Hazard Ratio [HR] = 2.6, p < 0.001). In the WHI CT validation population, it classified 8% of women as elevated risk, identifying 31% of cancers diagnosed within 7 years of enrollment (HR = 4.6, p < 0.001). Conclusion CA125 and HE4 contributed significantly to a risk prediction classifier combining serum markers with epidemiologic risk factors. The hybrid risk classifier may be useful to identify post-menopausal women who would benefit from timely surgical intervention to prevent epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Aflibercept targets vascular endothelial growth factor and placental growth factor. We evaluated activity and toxicity of aflibercept in recurrent/persistent endometrial cancer patients. Biomarkers and association with clinical characteristics and outcome were explored. Methods: Eligible patients had measurable disease; 1–2 prior cytotoxic regimens; performance status 0–2. Aflibercept 4mg/kg IV q14 days (28-day cycles) was administered until disease progression or prohibitive toxicity. Primary endpoints were the proportion of patients with progression-free survival at 6months (PFS6) and tumor response rate. A flexible two-stage group sequential design to detect 20% increases in the proportion of patients responding or enduring PFS6 with 90% power (α =10%) was employed. Results: Forty-nine patients were enrolled; five were excluded: wrong primary (2), second primary (1), wrong cell type (1); and never treated (1). Median age was 64 (range 48–83). Eighteen patients (41%) had two prior regimens; 27 (61%) had prior radiation. The PFS6 rate was 41%; three patients (7%, 90% CI: 2–17) had partial response. Of note, 10 patients (23%) met the PFS6 endpoint without starting a subsequent therapy; the remaining eight patients discontinued therapy for toxicity and started another therapy before 6months elapsed. Median PFS and overall survival were 2.9months and 14.6months, respectively. Significant grade 3/4 toxicities were: cardiovascular (23%/5%), constitutional (7%/0), hemorrhage (2%/5%), metabolic (7%/2%), and pain (18%/0). Two treatment-related deaths were recorded: GI perforation (1), and arterial rupture (1). FGF1 expression was associated with response. Conclusions: Aflibercept met pretrial activity parameters, but was associated with significant toxicity at this dose and schedule in this population. [Copyright &y& Elsevier]

Abstract: Purpose: This study sought to better understand the long-term effects on women''s health related quality of life (HRQOL) of involvement in decision-making about their surgical and chemotherapeutic treatments for ovarian cancer treatment and about follow-up care after treatment. Methods: Using a cross-sectional survey design, a sample of 219 ovarian cancer patient/survivors from Western Washington who were between 3months and ten years post-diagnosis were recruited via a mailed survey sent by their gynecological oncologist and interviewed about their ovarian cancer treatment, use of Complementary and Alternative Medicine (CAM), Health related quality of life, and their involvement in decision-making about their cancer treatment and follow-up care. Results: Multivariate regression analyses revealed age, but not stage of cancer to be a significant predictor of perceived involvement in decision-making about ovarian cancer treatment and follow-up. Age also predicted CAM use with older patients using herbal CAM, and younger patients using CAM activities and CAM providers (p<0.5). Controlling for demographic, disease, and treatment characteristics involvement in decision-making about surgery and follow-up care were associated with better mental health in survivorship (p<0.05). Involvement in decision-making about use of CAM and about lifestyle health changes was associated with greater vitality and better role-emotional health in survivorship (respectively; both; p<0.05). Conclusions: As has been found in studies of breast cancer survivors, perceived involvement in decision-making about ovarian cancer treatment including surgery and follow-up care after treatment is associated with better quality of life for cancer survivors. Involvement in decision-making about the use of CAM and about changes in lifestyle health practices also appear to help survivor''s emotional health related quality of life. Prospective studies are needed to determine the mechanisms by which perceived involvement in decision-making about treatment might influence survivor quality of life. [Copyright &y& Elsevier]

Abstract: Background. : Prior studies suggest that combining the Symptom Index (SI) with a serum HE4 test or a CA125 test may improve prediction of ovarian cancer. However, these three tests have not been evaluated in combination. Methods.: A prospective case–control study design including 74 women with ovarian cancer and 137 healthy women was used with logistic regression analysis to evaluate the independent contributions of HE4 and CA125, and the SI to predict ovarian cancer status in a multivariate model. The diagnostic performance of various decision rules for combinations of these tests was assessed to evaluate potential use in predicting ovarian cancer. Results. : The SI, HE4, and CA125 all made significant independent contributions to ovarian cancer prediction. A decision rule based on any one of the three tests being positive had a sensitivity of 95% with specificity of 80%. A rule based on any two of the three tests being positive had a sensitivity of 84% with a specificity of 98.5%. The SI alone had sensitivity of 64% with specificity of 88%. If the SI index is used to select women for CA125 and HE4 testing, specificity is 98.5% and sensitivity is 58% using the 2-of-3-positive decision rule. Conclusions. : A 2-of-3-positive decision rule yields acceptable specificity, and higher sensitivity when all 3 tests are performed than when the SI is used to select women for screening by CA125 and HE4. If positive predictive value is a high priority, testing by CA125 and HE4 prior to imaging may be warranted for women with ovarian cancer symptoms. [Copyright &y& Elsevier]

Abstract: Objective : Our objective was to characterize the expression and function of the miR-200 family of microRNAs (miRNA) in ovarian carcinogenesis. Methods : We used qRT-PCR to examine expression of the miR-200 miRNA family and its predicted targets, the ZEB1 and ZEB2 transcriptional repressors, in primary cultures of normal cells from the surface of the ovary and in a panel of 70 ovarian cancer tissues and 15 ovarian cancer cell lines. We studied the mechanisms of regulation of miR-200 miRNAs and ZEB transcription factors in ovarian cells using 3′ UTR luciferase reporters, promoter luciferase reporters and siRNAs. Results : miR-200 family members are expressed at low or negligible levels in normal ovarian surface cells and substantially increase in expression in ovarian cancer, whereas expression of ZEB1 and ZEB2 shows the opposite pattern. There is reciprocal repression between miR-200 family members and ZEB transcription factors, creating a double negative regulatory feedback loop resembling that reported in other cancer cell types. In contrast to epithelial cells from other sites, expression levels of miR-200 miRNAs and ZEB1/2 in cells from the ovarian surface are more consistent with a mesenchymal cell phenotype, potentially reflecting the mesothelial origin of the ovarian surface. Conclusion : Analysis of ovarian cancer tissues suggests that ovarian surface cells acquire a more epithelial miR-200-ZEB1/2 phenotype as they undergo transformation, switching from a miR-200 familyLOW and ZEB1/2HIGH state to a miR-200 familyHIGH and ZEB1/2LOW phenotype. Collectively, our data support the mesothelial-to-epithelial (Meso-E-T) model for development of ovarian cancers that arise from ovarian surface cells, as has been proposed previously on the basis of studies of protein markers. [Copyright &y& Elsevier]

Abstract: Objectives: Determine if cetuximab dose escalation to induce grade 2 rash correlates with anti-tumor activity and if sera-based markers could predict likelihood of response. Methods: Patients with persistent/recurrent ovarian or primary peritoneal carcinoma received an initial dose of cetuximab 400 mg/m2, then 250 mg/m2 weekly for two 3-week cycles. Patients who had stable disease (SD) and

: ObjectiveThe aim was to determine the response rate and toxicity of topotecan administered Days 1–3 every 21 days for recurrent epithelial cancers of the ovary, peritoneum, or fallopian tube. A 3-day regimen may be more convenient and less expensive than a 5-day schedule.: MethodsPatients with recurrent epithelial cancer of the ovary, peritoneum, or fallopian tube who had adequate hepatic, renal, and hematologic function were eligible for participation. Topotecan (2 mg/m2) was administered for 3 consecutive days every 21 days. Response was measured clinically and serologically. Granulocyte colony stimulating factors (GCSF) were not utilized prophylactically, but could be added under specific conditions.: ResultsThirty-one patients with recurrent ovarian cancer whose median age was 63 (range 32–84) received 165 cycles of topotecan (median = 6; range 2–8) and are evaluable for toxicity. The median number of prior regimens was 1. Topotecan was administered on schedule in 96.6% of cycles. Grade 3/4 neutropenia was seen in 29.1 and 23.6% of courses, respectively; but only 3.4% of cycles required GCSF support (6 cycles for 2 patients). Grade 4 thrombocytopenia was rare (1% of cycles). Nonhematologic toxicity was mild. The response rate for 28 evaluable patients was 32.1% (10.7% complete response (CR) and 21.4% partial response (PR)); stable disease was seen in 17.9% of patients. The median progression-free interval (PFI) for all patients was 15.5 weeks (range 5–40). Eighteen platinum-sensitive patients demonstrated a 43.4% response rate (12.5% CR and 31.3% PR); stable disease was documented in 18.8%. The median PFI for platinum-sensitive patients was 18.5 weeks (range 5–40).: ConclusionTopotecan is an effective regimen with acceptable toxicity for recurrent ovarian cancer when administered for 3 consecutive days (2 mg/m2) every 21 days. It can be delivered on schedule without GCSF support in the vast majority of patients. [Copyright &y& Elsevier]

Abstract: Background. : Malignant transformation of endometriosis is an infrequent complication of endometriosis. Extragonadal disease is uncommon. Case. : 55-year-old female presented with postmenopausal bleeding. Physical examination revealed a 2-cm polypoid lesion at the posterior vaginal apex, which was found to be a moderately differentiated invasive adenocarcinoma. Final pathology at the time of definitive surgery demonstrated a clear cell adenocarcinoma of the vagina arising in vaginal endometriosis. Conclusion. : Vaginal endometriosis may lead to the development of cancer. Malignancy arising in endometriotic foci is rare, but most commonly occurs in the ovary. We report a case of clear cell malignancy arising in vaginal endometriosis, adding to only seven cases previously reported. Risk factors include unopposed estrogen and obesity, but it may occur in the absence of either. [Copyright &y& Elsevier]