A novel early-stage orthotopic model for ovarian cancer in the Fischer 344 rat

The purpose of our study was to ascertain the progression of metastases in a novel ovarian cancer model designed to mimic early-stage disease by utilizing an orthotopic injection technique. Female Fischer 344 rats were injected with either 104 or 105 NuTu-19 cells by intraperitoneal or orthotopic injection. Peritoneal washings and histologic specimens were examined to correlate the incidence and extent of tumor growth. In a second phase, orthotopic injections of 102 and 103 cells were compared to that of 104 cells. Progression of ovarian cancer was observed by gross and microscopic examinations in both intraperitoneal and orthotopic models. Pelvic extension and abdominal adhesions uniquely characterized the orthotopically injected animals. Numbers of identifiable metastases declined with lower cell inocula, confirming that early-stage disease was extended to at least 14 days with 102 NuTu-19 cells. The orthotopic ovarian cancer model emulates early disease with the initiation of a primary tumor that is localized within the inherent microenvironment. The orthotopic model offers a clinically relevant alternative for future cancer research that allows for the investigation of therapeutic strategies against early stages of the disease process.

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BRAF Mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer

Cancer ◽

10.1002/cncr.27782 ◽

2012 ◽

Vol 119 (3) ◽

pp. 548-554 ◽

Cited By ~ 112

Author(s):

Rachel N. Grisham ◽

Gopa Iyer ◽

Karuna Garg ◽

Deborah DeLair ◽

David M. Hyman ◽

...

Keyword(s):

Ovarian Cancer ◽

Braf Mutation ◽

Early Stage ◽

Low Grade ◽

Serous Ovarian Cancer ◽

Early Stage Disease ◽

Stage Disease ◽

Improved Outcome

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A novel early-stage orthotopic model for ovarian cancer in the Fischer 344 rat

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2005.15211.x ◽

2005 ◽

Vol 15 (2) ◽

pp. 246-254 ◽

Cited By ~ 4

Author(s):

K.D Sloan Stakleff ◽

A.G Rouse ◽

A.P Ryan ◽

N.A Haller ◽

V.E. Von Gruenigen

Keyword(s):

Ovarian Cancer ◽

Early Stage ◽

Orthotopic Model ◽

Fischer 344 ◽

Fischer 344 Rat

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The relationship between tumor size and stage in early versus advanced ovarian cancer: A retrospective chart review

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5580 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5580-5580

Author(s):

L. E. Horvath ◽

T. Werner ◽

K. Jones

Keyword(s):

Ovarian Cancer ◽

Chart Review ◽

Advanced Disease ◽

Early Stage ◽

Abdominal Cavity ◽

Advanced Ovarian Cancer ◽

Retrospective Chart Review ◽

Advanced Stage ◽

Early Stage Disease ◽

Stage Disease

5580 Background: Ovarian cancer has a different prognosis between early (I and II) and advanced stage (III and IV). The mechanism of disease progression is unknown, but patients with advanced disease may have a higher propensity for seeding of the abdominal cavity early in the disease process than those with early stage. Theoretically if this is so, then patients with advanced stage should have smaller sized tumors than patients with early stage. Methods: This was a retrospective chart review of patients in the tumor registry in 2003 to 2006. Patients had epithelial ovarian cancer, other cell types were excluded. Only cases with documentation of surgical and pathologic staging and measured dimensions on pathologic specimen were included. Patient stage and all available dimensions measured on diseased ovaries were recorded. The dimensions for each patient were averaged into a single dimension for that patient, and then these measurements were totaled and averaged. Results: There were 110 patients analyzed: 85 with advanced disease, 25 with early stage. The average measurement was 4.8 cm in advanced disease, and was 10.7 cm in early stage disease. This difference was statistically significant (p < 0.001). Conclusions: Overall, patients with early stage ovarian cancer have diseased ovaries that are more than twice as large as those found in advanced disease. This finding supports the fact that early versus advanced ovarian cancer are 2 separate disease processes. Early stage grows locally and does not disseminate, and advanced stage disseminates while the tumor is still relatively small. Theoretically there may be a factor that separates these 2 into different diseases, where advanced disease patients have a substance produced by their tumor that allows for early dissemination, and early stage lacks this substance and only grows locally. Basic science research comparing the tissue microarrays of early versus advanced stage disease may be able to identify this difference. If the difference is found, perhaps therapy can be targeted against this difference. No significant financial relationships to disclose.

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Screening for ovarian cancer: Evidences

Nepalese Journal of Cancer ◽

10.3126/njc.v1i1.25620 ◽

2017 ◽

Vol 1 (1) ◽

pp. 1-7

Author(s):

Binuma Shrestha ◽

Bijaya Chandra Acharya

Keyword(s):

Ovarian Cancer ◽

Early Stage ◽

Abdominal Cavity ◽

Average Risk ◽

Preventive Healthcare ◽

Ovarian Cancer Screening ◽

Early Stage Disease ◽

Risk Result ◽

Stage Disease ◽

Increased Risk

Cancer of the ovary is a leading cause of death among women. Early stage disease are not evident for the incumbent nature of disease in the abdominal cavity. When ovarian cancer is detected and treated while it is still confined to the ovary (stage I), the 5-year survival rate is approximately 90%, but 33% when the disease is diagnosed at stage III or IV. So screening had role in down staging the disease and improve survival. Evidence still does not support screening in average risk women but annual gynecologic examination with pelvic examination is recommended for preventive healthcare. Screening in women with increased risk and inherited risk result in a decrease in the number of deaths in women. For women with mutations in BRCA2, ovarian cancer screening should be initiated between ages 35 and 40.

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Preoperative Sensitivity and Specificity for Early-Stage Ovarian Cancer When Combining Cancer Antigen CA-125II, CA 15-3, CA 72-4, and Macrophage Colony-Stimulating Factor Using Mixtures of Multivariate Normal Distributions

Journal of Clinical Oncology ◽

10.1200/jco.2004.03.091 ◽

2004 ◽

Vol 22 (20) ◽

pp. 4059-4066 ◽

Cited By ~ 108

Author(s):

Steven J. Skates ◽

Nora Horick ◽

Yinhua Yu ◽

Feng-Ji Xu ◽

Andrew Berchuck ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Stage ◽

Ca 125 ◽

Early Stage Disease ◽

Stage Disease ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Screening Sensitivity ◽

Stimulating Factor ◽

Combining Information

Purpose In CA-125–based ovarian cancer screening trials, overall specificity and screening sensitivity of ultrasound after an elevated CA-125 exceeded 99.6% and 70%, respectively, thereby yielding a positive predictive value (PPV) exceeding 10%. However, sensitivity for early-stage disease was only 40%. This study aims to increase preoperative sensitivity for early-stage ovarian cancer while maintaining the annual referral rate to ultrasound at 2% by combining information across CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor (M-CSF). For direct comparisons between marker panels, all sensitivity results correspond to a 98% fixed first-line specificity (referral rate 2%). Patients and Methods Logistic regression, classification tree, and mixture discriminant analysis (MDA) models were fit to a training data set of preoperative serum measurements (63 patients, 126 healthy controls) from one center. Estimates from the training set applied to an independent validation set (60 stage I to II patients, 98 healthy controls) from two other centers provided unbiased estimates of sensitivity. Results Preoperative sensitivities for early-stage disease of the optimal panels were 45% for CA-125II; 67% for CA-125II and CA 72-4; 70% for CA-125II, CA 72-4, and M-CSF; and 68% for all four markers (latter two results using MDA). Conclusion Efficiently combining information on CA-125II, CA 72-4, and M-CSF significantly increased preoperative early-stage sensitivity from 45% with CA-125II alone to 70%, while maintaining 98% first-line specificity. Screening trials with these markers using MDA followed by referral to ultrasound may maintain previously high levels of specificity and PPV, while significantly increasing early-stage screening sensitivity. MDA is a useful, biologically justified method for combining biomarkers.

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Mucinous ovarian cancer

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2007.01022.x ◽

2008 ◽

Vol 18 (2) ◽

pp. 209-214 ◽

Cited By ~ 40

Author(s):

M. L. Harrison ◽

C. Jameson ◽

M. E. Gore

Keyword(s):

Ovarian Cancer ◽

Clinical Presentation ◽

Early Stage ◽

Relative Resistance ◽

Genetic Studies ◽

Early Stage Disease ◽

Histologic Subtype ◽

Stage Disease ◽

Relative Rarity ◽

Ovarian Involvement

Mucinous epithelial ovarian cancer (mEOC) accounts for approximately 10% of EOCs. Patients presenting with early-stage disease have an excellent prognosis, however, those with advanced disease have a poor outcome with relative resistance to standard ovarian cancer chemotherapy. Molecular and genetic studies demonstrate differences between mucinous and serous EOC supporting the concept that these tumors develop along separate pathways. Together with the observed differences in clinical behavior and outcome for mEOC, there is a need to develop specific therapeutic strategies for this histologic subtype. The relative rarity of advanced mEOC has resulted in few patients enrolled in major ovarian cancer trials. The results of such trials may not necessarily reflect those specific to mEOC. Separate trials testing alternative chemotherapeutics are required. Metastatic mucinous tumors from other sites such as the gastrointestinal tract may present with ovarian involvement. For all mucinous tumors of the ovary, establishing primary as opposed to metastatic cancers is important. Clinical presentation, tumor markers, histologic, and immunohistochemical features are helpful in distinguishing most cases.

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Screening methods of ovarian cancer in adults

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0502072m ◽

2005 ◽

Vol 133 (1-2) ◽

pp. 72-75 ◽

Cited By ~ 2

Author(s):

Vera Milenkovic ◽

Radmila Sparic ◽

Jasmina Atanackovic

Keyword(s):

Ovarian Cancer ◽

High Mortality ◽

Early Stage ◽

Uterine Cancer ◽

Direct Result ◽

High Risk Population ◽

Screening Methods ◽

Ovarian Cancer Screening ◽

Early Stage Disease ◽

Stage Disease

Ovarian cancer is associated with high mortality rate which has improved a little despite therapeutic advances. It causes more deaths than combined cervical and uterine cancer. High mortality is believed to be a direct result of already advanced stage at the time of diagnosis. Survival is excellent in case of early stage disease but poor in late stage disease, regardless of histology. The goal of screening for ovarian cancer is restricted to detection of asymptomatic early stage disease, as precursor lesions of ovarian cancer have not been identified. At present, there is no reliable method of ovarian cancer screening which has been shown to reduce mortality from ovarian cancer. Therefore, routine screening of women in general population can not be currently advised. Screening should be limited to high-risk population and subjects participating in research projects as long as the results of current studies are available.

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Patterns of care for women with ovarian cancer in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.11.3408 ◽

1997 ◽

Vol 15 (11) ◽

pp. 3408-3415 ◽

Cited By ~ 104

Author(s):

K A Muñoz ◽

L C Harlan ◽

E L Trimble

Keyword(s):

Ovarian Cancer ◽

Older Women ◽

Early Stage ◽

Stage Iv ◽

The United States ◽

Stage I ◽

Stage Iii ◽

Early Stage Disease ◽

Stage Disease ◽

Platinum Based Chemotherapy

PURPOSE To characterize treatments for ovarian cancer, to determine if recommended staging and treatment were provided, and to determine factors that influence receipt of recommended staging and treatment. METHODS A total of 785 women diagnosed with ovarian cancer in 1991 were selected from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program. Type and receipt of recommended staging and treatment were examined using data on surgery and physician-verified chemotherapy. RESULTS Most women with presumptive stage I and II ovarian cancer were treated with surgery alone (58%), while women with stage III or IV disease were treated with surgery plus platinum-based chemotherapy (75% stage III, 56% stage IV). Approximately 10% of women with presumptive stage I and II, 71% with stage III, and 53% with stage IV disease received recommended staging and treatment. The absence of lymphadenectomy and assignment of histologic grade were the primary reasons women with presumptive stage I and II cancer did not receive recommended staging and treatment, whereas for stages III and IV, it was due to older women not receiving surgery plus platinum-based adjuvant chemotherapy. Age, stage, comorbidity, "other" race/ethnicity, and treatment at a facility with an approved residency training program were associated with whether recommended staging and therapy were received. CONCLUSION Older women with late-stage disease did not receive recommended treatment. The majority of women with early-stage disease did not receive recommended staging and treatment.

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The Role of CA 125 in Screening for Ovarian Cancer

The International Journal of Biological Markers ◽

10.1177/172460089801300408 ◽

1998 ◽

Vol 13 (4) ◽

pp. 216-220 ◽

Cited By ~ 30

Author(s):

A.N. Rosenthal ◽

I.J. Jacobs

Keyword(s):

Ovarian Cancer ◽

Early Stage ◽

Survival Rates ◽

Ca 125 ◽

Early Stage Disease ◽

Mathematical Algorithm ◽

Gynaecological Malignancy ◽

Stage Disease ◽

Screening Strategies ◽

Randomised Controlled

Ovarian cancer has the worst prognosis of any gynaecological malignancy, primarily because it tends to present at an advanced stage. The excellent survival rates of early stage disease have provided the rationale for efforts to detect ovarian cancer early by screening, in the hope that survival rates will be improved. Available data suggests that CA 125 is elevated in the majority of epithelial ovarian malignancies prior to clinical presentation. Large trials of screening for ovarian cancer indicate that using a CA 125 cutoff value of 30 U/mL has good sensitivity, but inadequate specificity for detecting preclinical disease. Use of transvaginal ultrasonography as a second-line test in women with elevated CA 125 levels improves specificity to acceptable levels, as does use of a mathematical algorithm which analyses rates of change of CA 125. Two major randomised controlled trials, investigating the effect of screening strategies incorporating CA 125 on mortality, are currently underway.

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