Edmonston vaccine strains of measles virus (MV) have shown significant antitumor activity in preclinical models of ovarian cancer. We engineered MV to express the marker peptide carcinoembryonic antigen (MV-CEA virus) to also permit real-time monitoring of viral gene expression in tumors in the clinical setting. Patients with Taxol and platinum-refractory recurrent ovarian cancer and normal CEA levels were eligible for this phase I trial. Twenty-one patients were treated with MV-CEA i.p. every 4 weeks for up to 6 cycles at seven different dose levels (10 3 -10 9 TCID 50 ). We observed no dose-limiting toxicity, treatment-induced immunosuppression, development of anti-CEA antibodies, increase in anti-MV antibody titers, or virus shedding in urine or saliva. Dose-dependent CEA elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of patient tumor specimens revealed overexpression of measles receptor CD46 in 13 of 15 patients. Best objective response was dose-dependent disease stabilization in 14 of 21 patients with a median duration of 92.5 days (range, 54-277 days). Five patients had significant decreases in CA-125 levels. Median survival of patients on study was 12.15 months (range, 1.3-38.4 months), comparing favorably to an expected median survival of 6 months in this patient population. Our findings indicate that i.p. administration of MV-CEA is well tolerated and results in dose-dependent biological activity in a cohort of heavily pretreated recurrent ovarian cancer patients. Cancer Res; 70(3); 875-82. ©2010 AACR.

Objective To estimate lower-extremity lymphedema prevalence in patients surgically treated for endometrial cancer, identify predictors of lymphedema, and evaluate the effects of lymphedema on quality of life. Methods One thousand forty-eight consecutive patients who were operated on between 1999 and 2008 at Mayo Clinic were mailed a survey, which included our validated 13-item lymphedema screening questionnaire and two validated quality-of-life measures. Logistic regression models were fit to identify factors associated with prevalent lymphedema; a multivariable model was obtained using stepwise and backward variable selection methods. The relationship between lymphedema and obesity with each quality-of-life score was evaluated in a separate multivariable linear model. Results There were 591 responders (56%) after exclusions. Our questionnaire revealed a previous self-reported lymphedema diagnosis in 103 (17%) patients and identified undiagnosed lymphedema in 175 (30%) (overall prevalence 47.0%; median 6.2 years follow-up). Lymphedema prevalence in patients treated with hysterectomy alone compared with lymphadenectomy was 36.1% and 52.3%, respectively (attributable risk, 23%). Lymphedema risk was not associated with the number of nodes removed or the extent of lymphadenectomy after adjusting for other factors. On multivariable analysis, higher BMI, congestive heart failure, performance of lymphadenectomy, and radiation therapy were associated with prevalent lymphedema. Multiple quality-of-life scores were worse in women with lymphedema. Conclusion The attributable risk of developing lower-extremity lymphedema was 23% for patients with endometrial cancer who underwent lymphadenectomy compared to hysterectomy alone, with an overall prevalence of 47%. Lymphedema was associated with reductions in multiple quality-of-life domains.

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Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms most commonly occurring in the gastrointestinal tract or the lungs. More frequent are gastrointestinal tumors, but over the past 30 years, there have been a number of small series or anecdotal case reports on ovarian NETs. Neuroendocrine tumors in the gynecologic tract are uncommon and account for about 2% of all gynecologic malignancies but may also be metastatic from other sites. They require a multimodality therapeutic approach determined by the extent of disease and the primary organ of involvement. Pathological diagnosis is critical to guide therapy. Surgery is the cornerstone of treatment for localized disease. There have been many new developments for treatment of advanced NETs including somatostatin analogs, hepatic artery embolization, chemotherapy, interferons, mammalian target of rapamycin inhibitors and radiolabeled somatostatin analogs. Given the rarity and lack of level I evidence, this is by nature more of a guidance and recommendation for management of these rare tumors until we can mount international studies.