G. Scott Rose

Tumor Residual After Surgical Cytoreduction in Prediction of Clinical Outcome in Stage IV Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

PURPOSE To identify factors predictive of poor prognosis in a similarly treated population of women with stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS A retrospective review of 360 patients with International Federation of Gynecology and Obstetrics stage IV EOC who underwent primary surgery followed by six cycles of intravenous platinum/paclitaxel was performed. A proportional hazards model was used to assess the association of potential prognostic factors with progression-free survival (PFS) and overall survival (OS). RESULTS The median PFS and OS for this group of stage IV ovarian cancer patients was 12 and 29 months, respectively. Multivariate regression analysis revealed that histology, malignant pleural effusion, intraparenchymal liver metastasis, and residual tumor size were significant prognostic variables. Whereas patients with microscopic residual disease had the best outcome, patients with 0.1 to 1.0 cm residual disease and patients with 1.1 to 5.0 cm residual disease had similar PFS and OS. Patients with a residual size more than 5 cm had a diminished PFS and OS when compared with all other groups. Median OS for microscopic, 0.1 to 5.0 cm, and more than 5.0 cm residual disease was 64, 30, and 19 months, respectively. CONCLUSION Patients with more than 5 cm residual disease have the shortest PFS and OS, whereas patients with 0.1 to 1.0 and 1.1 to 5.0 cm have similar outcome. These findings suggest that ultraradical cytoreductive procedures might be targeted for selected patients in whom microscopic residual disease is achievable. Patients with less than 5.0 cm of disease initially and significant disease and/or comorbidities precluding microscopic cytoreduction may be considered for alternative therapeutic options other than primary cytoreduction.

Expression Profiling Identifies Altered Expression of Genes That Contribute to the Inhibition of Transforming Growth Factor-β Signaling in Ovarian Cancer

Ovarian cancer is resistant to the antiproliferative effects of transforming growth factor-beta (TGF-beta); however, the mechanism of this resistance remains unclear. We used oligonucleotide arrays to profile 37 undissected, 68 microdissected advanced-stage, and 14 microdissected early-stage papillary serous cancers to identify signaling pathways involved in ovarian cancer. A total of seven genes involved in TGF-beta signaling were identified that had altered expression >1.5-fold (P < 0.001) in the ovarian cancer specimens compared with normal ovarian surface epithelium. The expression of these genes was coordinately altered: genes that inhibit TGF-beta signaling (DACH1, BMP7, and EVI1) were up-regulated in advanced-stage ovarian cancers and, conversely, genes that enhance TGF-beta signaling (PCAF, TFE3, TGFBRII, and SMAD4) were down-regulated compared with the normal samples. The microarray data for DACH1 and EVI1 were validated using quantitative real-time PCR on 22 microdissected ovarian cancer specimens. The EVI1 gene locus was amplified in 43% of the tumors, and there was a significant correlation (P = 0.029) between gene copy number and EVI1 gene expression. No amplification at the DACH1 locus was found in any of the samples. DACH1 and EVI1 inhibited TGF-beta signaling in immortalized normal ovarian epithelial cells, and a dominant-negative DACH1, DACH1-Delta DS, partially restored signaling in an ovarian cancer cell line resistant to TGF-beta. These results suggest that altered expression of these genes is responsible for disrupted TGF-beta signaling in ovarian cancer and they may be useful as new and novel therapeutic targets for ovarian cancer.

Adenosquamous histology predicts a poor outcome for patients with advanced-stage, but not early-stage, cervical carcinoma†‡

The objective of this study was to compare survival between patients with adenocarcinoma and patients with adenosquamous carcinoma of the cervix.

Racial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma: a Gynecologic Oncology Group study.

Previous studies have reported shorter survival of black women compared with white women who had advanced/recurrent endometrial cancer. It has been suggested that this may reflect racially based differences in treatment.

Intraperitoneal bevacizumab for the palliation of malignant ascites in refractory ovarian cancer

BACKGROUND Malignant ascites often has a profound impact on the quality of life of patients with refractory ovarian cancer. Current treatments, including dietary, medical, and procedural are often temporary and unsatisfactory options in patients approaching the end of life. CASE We present a case of an 88 year-old receiving home hospice care with refractory ovarian cancer and severe symptomatic ascites. We performed a paracentesis and treated her with intraperitoneal bevacizumab with dramatic improvement in her ascites and the quality of her final weeks of life. CONCLUSION Intraperitoneal bevacizumab may be a useful tool in the palliation of malignant ascites and is worthy of further study.

Prognosis and recurrence risk for patients with cervical squamous intraepithelial lesions diagnosed during pregnancy

In the current study, the authors sought to examine the prognosis and recurrence risk for patients with cervical squamous intraepithelial lesions (SILs) diagnosed during pregnancy.

Racial disparities in blacks with gynecologic cancers.

Black women have a lower incidence of gynecologic cancers but they have a higher mortality associated with their disease. The etiology of the racial disparity in outcome among gynecologic cancer patients is multifactoral and site‐specific. Black women with endometrial cancer often present with more advanced stage tumors that are associated with a worse prognosis compared with White women. Evidence suggests that observed disparities in outcome are due to inequalities in treatment or differing biologic etiologies. For cervix cancer, studies have suggested that survival among Black women may be lower than survival among White women that develop this disease. This occurs despite evidence that indicates that Pap smears are utilized similarly by Black and White women for cervix cancer screening. These differences in outcome may become less pronounced when comorbidities are accounted for and inequalities in treatment are eliminated. For ovarian cancer patients, survival has improved with the use of contemporary therapies over the past 30 years in Whites but less so for Blacks. This may be due to differences in the likelihood of primary surgical cytoreductions, which are performed less frequently in some Black women because of extensive metastatic spread or comorbidities. The observed decreases in survival for all 3 gynecologic cancers potentially may be affected by socioeconomic status of the patient in some healthcare settings. An improved understanding of the causative factors associated with racial disparities in gynecologic cancer outcome is necessary to facilitate efforts aimed at correcting this important healthcare problem. Cancer 2007.

Cost-effectiveness analysis of liquid-based cytology and human papillomavirus testing in cervical cancer screening

OBJECTIVE: To compare the outcomes of several cervix cancer screening strategies in a military population using a model that considers both direct and indirect costs of health care. METHODS: A Markov model of the natural history of cervical cancer was used to simulate an age-stratified cohort of 100,000 active duty women in the U.S. Army. Total costs and incremental cost-effectiveness ratios were estimated for different modalities of screening: liquid-based cytology with testing for human papillomavirus (HPV) irrespective of cytologic results compared with liquid-based cytology with HPV detection for cytologic results of atypical cells of undetermined significance (reflex HPV). The costs and outcomes of these screening methods were evaluated separately as well as in combination (liquid-based cytology and reflex HPV before age 30 years and DNA and Pap test every 3 years thereafter). Each of these screening methods was evaluated at 1-, 2-, and 3-year intervals. RESULTS: A screening strategy of liquid-based cytology and reflex HPV every 2 or 3 years is the least costly strategy among active duty women irrespective of age, especially when accounting for time costs associated with screening, diagnosis, and treatment of cervix cancer. A strategy of liquid-based cytology and HPV testing irrespective of cytology results is the most effective strategy; however, it is also the most costly of the strategies tested, even when performed in patients older than 30 years of age. CONCLUSION: In the U.S. Army, cervix cancer screening performed with liquid-based cytology and reflex HPV testing of atypical squamous cells of undetermined significance performed every 2 years is cost-effective, especially when indirect costs are considered. LEVEL OF EVIDENCE: III

Costs and effectiveness of alternative strategies for cervical cancer screening in military beneficiaries.

OBJECTIVE To estimate the potential effects, on costs and outcomes, of changes in sensitivity and specificity associated with new screening methods for cervical cancer in the military. METHODS A Markov model of the natural history of cervical cancer was created to simulate a cohort of 100,000 military beneficiaries aged 18–85. Probability estimates for various outcomes and the accuracy of screening tests were obtained from the literature. Cost estimates were obtained from military sources where available; otherwise, civilian costs were used. The outcomes and costs of conventional cytology, liquid‐based cytology, and liquid‐based cytology with human papillomavirus (HPV) triage were compared at 1‐, 2‐, and 3‐year screening frequencies. RESULTS Marginal reductions in the incidence of cervical cancer from increasing screening sensitivity are greater than reductions in cancer mortality at every screening interval. Incremental improvements in both cancer incidence and mortality are higher at less frequent screening intervals. Increases in the ratio of low‐ to high‐grade lesions result from increasing the sensitivity of the screening test or shortening the screening interval. Both liquid‐based cytology and liquid‐based cytology with HPV testing are cost effective (less than

The impact of disease distribution on survival in patients with stage III epithelial ovarian cancer cytoreduced to microscopic residual: A gynecologic oncology group study

50,000 per life‐year saved) when performed at 3‐year screening intervals. However, neither strategy is cost‐effective when performed more frequently than every 3 years. CONCLUSION Use of a more sensitive cervical cancer screening test increases costs. However, a more sensitive test performed less frequently may be more effective and less expensive than conventional cytology done annually. In the military setting, this has significant implications for both expense reduction and readiness enhancement.