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ABSTRACT: Ovarian cancer is usually diagnosed at an advanced stage, rendering the possibility of cure unlikely. To date, no cost-effective screening test has proven effective for reducing mortality. To estimate the window of opportunity for ovarian cancer screening, we develop a branching process model for ovarian cancer growth and progression accounting for three cell populations: Primary (cells in the ovary or fallopian tube), Peritoneal (viable cells in peritoneal fluid), and Metastatic (cells implanted on other intra-abdominal surfaces). Growth and migration parameters were chosen to match results of clinical studies. Using these values, our model predicts a window of opportunity of 2.9 years, indicating that one would have to screen at least every other year to be effective. The model can be used to inform future efforts in designing improved screening and treatment strategies.
Journal of Theoretical Biology 08/2012; 314:10-5. · 2.21 Impact Factor
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ABSTRACT: In this chapter, we summarise findings from recent cost-effectiveness analyses of screening for cervical cancer and ovarian cancer. We begin with a brief summary of key issues that affect the cost-effectiveness of screening, including disease burden, and availability and type of screening tests. For cervical cancer, we discuss the potential effect of human papilloma virus vaccines on screening. Outstanding epidemiological and cost-effectiveness issues are included. For cervical cancer, this includes incorporating the long-term effect of treatment (including adverse birth outcomes in treated women who are of reproductive age) into cost-effectiveness models using newly available trial data to identify the best strategy for incorporating human papilloma virus tests. A second issue is the need for additional data on human papilloma virus vaccines, such as effectiveness of reduced cancer incidence and mortality, effectiveness in previously exposed women and coverage. Definitive data on these parameters will allow us to update model-based analyses to include more realistic estimates, and also potentially dramatically alter our approach to screening. For ovarian cancer, outstanding issues include confirming within the context of a trial that screening is effective for reducing mortality and incorporating tests with high specificity into screening into screening algorithms for ovarian cancer.
Best practice & research. Clinical obstetrics & gynaecology 12/2011; 26(2):163-73. · 1.87 Impact Factor
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ABSTRACT: To compare the practices, adjuvant treatment, and outcomes of patients with preoperatively assessed grade 1 endometrioid endometrial cancer between two academic gynecologic oncology centers that use different treatment strategies.
A retrospective analysis was performed at Duke University Medical Center (Duke) and the Toronto Sunnybrook Regional Cancer Center (Sunnybrook) between 1991 and 2007. Patients at Duke generally underwent surgical staging unless intraoperative assessment identified a negligible risk of nodal disease. Patients at Sunnybrook generally did not undergo surgical staging.
A total of 494 patients (272 from Duke and 222 from Sunnybrook were identified with preoperative, central-review-confirming, grade 1, endometrioid, endometrial cancer. Groups were similar in grade, final histology, type of hysterectomy, and length of hospital stay. Patients from Sunnybrook were older (aged 62 years compared with 59 years, P=.001) and were more likely to have capillary lymphatic space involvement (18.2% compared with 8.3%, P=.003) and cervical involvement (12.2% compared with 3.7%, P<.001). Approximately 2% of cases were upgraded to high grade on final specimen. Lymphadenectomy was performed on 49.4% of patients at Duke compared with 11.7% of patients at Sunnybrook. Overall 3-year survival was 96% at Duke and 96% at Sunnybrook (P=.217). Three-year recurrence-free survival was 96% at Duke and 95% at Sunnybrook (P=.327).
Despite differences in practice and slight differences in patient populations, the recurrence-free and overall survival of women with preoperative centrally reviewed grade 1 endometrial cancer is excellent and without statistically significant difference between the two centers.
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Obstetrics and Gynecology 07/2009; 114(1):7-15. · 4.73 Impact Factor
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ABSTRACT: We wished to determine whether a pre-existing diagnosis of breast cancer or the use of tamoxifen among patients with pre-existing breast cancer influences the histologic type of subsequently diagnosed endometrial carcinoma, the interval between these diagnoses, or survival.
A single institution retrospective review was performed of all patients who underwent primary surgery for endometrial carcinoma from 1995-2005. We compared the histologic type of endometrial carcinoma among patients with a prior history of breast cancer to those without. Patients with a previous diagnosis of breast cancer were further analyzed by comparing histologic type, progression-free and overall survival between tamoxifen users and non-users.
Among 732 women with endometrial carcinoma, 59 patients (8%) had a previous diagnosis of breast cancer, of whom 29 (49%) had used tamoxifen. Women with a history of breast cancer were more likely to have a high risk uterine histologic type (grade 3 endometrioid, papillary serous, or clear cell) (18/59; 31%) than those without this prior malignancy (120/670, 18%; p=0.024). Breast cancer survivors whose endometrial carcinoma was of a high risk histologic type had a longer median duration of prior tamoxifen use compared to those with lower risk histologic types (60 versus 46 months, p=0.034).
Among women with endometrial carcinoma, those with a history of breast cancer are more likely to harbor a high risk uterine histologic subtype. Tamoxifen use of at least 60 months is associated with high risk uterine histologic subtypes when compared to no tamoxifen use. This study adds to existing data suggesting a relationship between tamoxifen use and development of endometrial carcinoma of more aggressive histologic types.
Gynecologic Oncology 11/2008; 112(1):150-4. · 3.89 Impact Factor
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John P Kirkpatrick,
Zahid N Rabbani,
Rex C Bentley,
Matt E Hardee,
Seth Karol,
Jeffrey Meyer,
Egbert Oosterwijk, Laura Havrilesky,
Angeles Alvarez Secord,
Zeljko Vujaskovic,
Mark W Dewhirst,
Ellen L Jones
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ABSTRACT: Tumor hypoxia is associated with adverse outcome in many malignancies. The goal of this study was to determine if elevated expression of carbonic anhydrase IX (CAIX), a biomarker of hypoxia, predicts for recurrence in early-stage cervical cancer. The charts of all patients with early-stage cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed. Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remained disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/intensity of staining. Outcome, as measured by freedom from recurrence (FFR), distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastases as first site of failure (5-year FFDM 50%) than patients with only +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p = 0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expression is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.
Biomarker insights 02/2008; 3:45-55.
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ABSTRACT: To identify gene expression patterns that characterize advanced stage serous ovarian cancers by using microarray expression analysis.
Using genome-wide expression analysis, we compared a series of 31 advanced stage (III or IV) serous ovarian cancers from patients who survived either less than 2 years or more than 7 years with three normal ovarian epithelial samples. Array findings were validated by analysis of expression of the insulin-like growth factor binding protein 2 (IGFBP2) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) genes using quantitative real-time polymerase chain reaction (QRT-PCR).
Hierarchical clustering identified patterns of gene expression that distinguished cancer from normal ovarian epithelium. We also identified gene expression patterns that distinguish cancers on the basis of patient survival. These genes include many that are associated with immune function. Expression of IGFBP2 and TRAIL genes measured by array and QRT-PCR analysis demonstrated correlation coefficients of 0.63 and 0.78, respectively.
Global expression analysis can identify expression patterns and individual genes that contribute to ovarian cancer development and outcome. Many of the genes that determine ovarian cancer survival are associated with the immune response, suggesting that immune function influences ovarian cancer virulence. With the generation of newer arrays with more transcripts, larger studies are possible to fully characterize genetic signatures that predict survival that may ultimately be used to guide therapeutic decision-making.
Journal of the Society for Gynecologic Investigation 02/2004; 11(1):51-9. · 2.26 Impact Factor
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ABSTRACT: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol.
Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor.
There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P =.014) and a 60% reduction in risk of disease progression (P =.014) for women with such mutations. However, these striking risk reductions increased over time (P <.02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100%) with only missense mutation(s), seven patients (32%) with truncation mutations, and eight patients (40%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome.
Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome.
Journal of Clinical Oncology 10/2003; 21(20):3814-25. · 18.37 Impact Factor
