The survival detriment of venous thromboembolism with epithelial ovarian cancer.

OBJECTIVE: The aim of this study is to evaluate the effect of venous thromboembolism (VTE) chronology with respect to surgery on survival with epithelial ovarian cancer (EOC). METHODS: An IRB approved, retrospective review was performed of patients treated for Stage I-IV EOC from 1996 to 2011. Cox proportional hazards model was used to assess associations between VTE and the primary outcomes of progression free survival (PFS) and overall survival (OS). SAS 9.3 was used for statistical analyses. RESULTS: 586 patients met study criteria. Median age was 63 years (range, 17-94); median BMI was 27.1 kg/m(2) (range, 13.7-67.0). Most tumors were high grade serous (68.3%) and advanced stage (III/IV, 75.4%). 3.7% had a preoperative VTE; 13.2% had a postoperative VTE. Upon multivariate analysis adjusting for age, stage, histology, performance status, and residual disease, preoperative VTE was predictive of OS (HR 3.1, 95% CI: 1.6-6.1, p=0.001) but not PFS (p=0.55). Postoperative VTE was associated with shorter PFS (HR 1.45, 95% CI: 1.04-2.02, p=0.03) and OS (HR 1.8, 95% CI: 1.3-2.6, p=0.001). When VTE timing was modeled, preoperative VTE (HR 3.5, 95% CI: 1.8-6.9, p<0.001) and postoperative VTE after primary therapy (HR 2.3, 95% CI: 1.4-3.6, p=0.001) were predictive of OS. CONCLUSION: Preoperative and postoperative VTE appear to have a detrimental effect on OS with EOC. When modeled as a binary variable, postoperative VTE attenuated PFS; however, when VTE timing was modeled, postoperative VTE was not associated with PFS. It is unclear whether VTE is an inherent poor prognostic marker or if improved VTE prophylaxis and treatment may enable similar survival to patients without these events.

Outcomes of cervical cancer and positive para-aortic lymph nodes in the modern era of chemoradiation.

OBJECTIVE: Patients with cervical cancer with positive para-aortic lymph nodes have a poor prognosis. Our primary aim was to describe outcomes among this subgroup in the era of modern chemoradiation. METHODS: Patients with histologically confirmed cervical cancer metastatic to their para-aortic lymph nodes diagnosed between 1998 and 2011 and treated with curative intent were included in this analysis. Surgicopathologic, demographic, and outcome data were collected. Descriptive and survival statistics were generated to evaluate overall survival (OS) and progression-free survival (PFS) and to compare outcomes by treatment. P values were generated using both Wilcoxon and log-rank methods and listed respectively. RESULTS: The median PFS was 19 months. The median OS was 23.4 months. The median PFS for radiation only was 14 months and for chemoradiation was 20 months (P = 0.27 and 0.60, respectively). There was no difference in median OS for the radiation-only group versus chemoradiation. The median OS stratified by stage was 32 months (stage I), 21 months (stage II), 19.4 months (stage III), and 19.8 months (stage IV; P = 0.17 and 0.22). CONCLUSIONS: Our study shows a median OS of 23 months, which is less than what was documented in the literature. Despite the use of modern chemoradiation therapy, most of the cohort died within 3 years. The low OS presented in our study highlights the limitations of the current treatment regimens and the need for identification of for more effective therapy.

Inpatient versus outpatient management of neutropenic fever in gynecologic oncology patients: is risk stratification useful?

OBJECTIVE: This study aimed to evaluate the utility of risk stratification of gynecologic oncology patients with neutropenic fever (NF). METHODS: A retrospective chart review of gynecologic cancer patients admitted with NF from 2007 to 2011 was performed, wherein demographic, oncologic, and NF characteristics (hospitalization length, complications, and death) were collected. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score was calculated; low risk was considered ≥ 21. SAS 9.2 was used for statistical analyses. RESULTS: Eighty-three patients met the study criteria. Most (92%) were Caucasian and had advanced stage disease (71%). Primary tumors were 58% ovary, 35% endometrium, and 6% cervix. All patients were receiving chemotherapy on admission (72% for primary, 28% for recurrent disease). Forty-eight percent had a positive culture, and most (58%) positive cultures were urine. Seventy-six percent of patients were considered low risk. High-risk patients were more likely to have a severe complication (10% versus 50%, p=0.0003), multiple severe complications (3% versus 20%, p=0.0278), ICU admission (2% versus 40%, p<0.0001), overall mortality (2% versus 15%, p=0.0417), and death due to neutropenic fever (0% versus 15%, p=0.0124). MASCC had a positive predictive value of 50% and negative predictive value of 90%. The median MASCC score for all patients was 22 (range, 11-26), but the median MASCC score for those with death or a severe complication was 17 (range, 11-24). CONCLUSION: Based on this pilot data, MASCC score appears promising in determining suitability for outpatient management of NF in gynecologic oncology patients. Prospective study is ongoing to confirm safety and determine impact on cost.

Generation of competent bone marrow-derived antigen presenting cells from the deer mouse (Peromyscus maniculatus).

BACKGROUND: Human infections with Sin Nombre virus (SNV) and related New World hantaviruses often lead to hantavirus cardiopulmonary syndrome (HCPS), a sometimes fatal illness. Lungs of patients who die from HCPS exhibit cytokine-producing mononuclear infiltrates and pronounced pulmonary inflammation. Deer mice (Peromyscus maniculatus) are the principal natural hosts of SNV, in which the virus establishes life-long persistence without conspicuous pathology. Little is known about the mechanisms SNV employs to evade the immune response of deer mice, and experimental examination of this question has been difficult because of a lack of methodologies for examining such responses during infection. One such deficiency is our inability to characterize T cell responses because susceptible syngeneic deer mice are not available. RESULTS: To solve this problem, we have developed an in vitro method of expanding and generating competent antigen presenting cells (APC) from deer mouse bone marrow using commercially-available house mouse (Mus musculus) granulocyte-macrophage colony stimulating factor. These cells are capable of processing and presenting soluble protein to antigen-specific autologous helper T cells in vitro. Inclusion of antigen-specific deer mouse antibody augments T cell stimulation, presumably through Fc receptor-mediated endocytosis. CONCLUSIONS: The use of these APC has allowed us to dramatically expand deer mouse helper T cells in culture and should permit extensive characterization of T cell epitopes. Considering the evolutionary divergence between deer mice and house mice, it is probable that this method will be useful to other investigators using unconventional models of rodent-borne diseases.