Assessment of published models and prognostic variables in epithelial ovarian cancer at Mayo Clinic

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Abstract

Objectives

Epithelial ovarian cancer (EOC) is an aggressive disease in which first line therapy consists of a surgical staging/debulking procedure and platinum based chemotherapy. There is significant interest in clinically applicable, easy to use prognostic tools to estimate risk of recurrence and overall survival. In this study we used a large prospectively collected cohort of women with EOC to validate currently published models and assess prognostic variables.

Methods

Women with invasive ovarian, peritoneal, or fallopian tube cancer diagnosed between 2000-2011 and prospectively enrolled into the Mayo Clinic Ovarian Cancer registry were identified. Demographics and known prognostic markers as well as epidemiologic exposure variables were abstracted from the medical record and collected via questionnaire. Six previously published models of overall and recurrence-free survival were assessed for external validity. In addition, predictors of outcome were assessed in our dataset.

Results

Previously published models validated with a range of c-statistics (0.587-0.827), though application of models containing variables not part of routine practice were somewhat limited by missing data; utilization of all applicable models and comparison of results is suggested. Examination of prognostic variables identified only the presence of ascites and ASA score to be independent predictors of prognosis in our dataset, albeit with marginal gain in prognostic information, after accounting for stage and debulking.

Conclusions

Existing prognostic models for newly diagnosed EOC showed acceptable calibration in our cohort for clinical application. However, modeling of prospective variables in our dataset reiterates that stage and debulking remain the most important predictors of prognosis in this setting.

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Most cited references 17

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Regression Modeling Strategies

Frank E. Harrell (2001)

Springer Series in Statistics

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Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls.

V Beral, R Doll, C Hermon … (2008)

Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We aimed to assess these effects. Individual data for 23,257 women with ovarian cancer (cases) and 87,303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use was estimated, stratifying by study, age, parity, and hysterectomy. Overall 7308 (31%) cases and 32,717 (37%) controls had ever used oral contraceptives, for average durations among users of 4.4 and 5.0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average of 56 years. The longer that women had used oral contraceptives, the greater the reduction in ovarian cancer risk (p<0.0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased but became somewhat attenuated over time-the proportional risk reductions per 5 years of use were 29% (95% CI 23-34%) for use that had ceased less than 10 years previously, 19% (14-24%) for use that had ceased 10-19 years previously, and 15% (9-21%) for use that had ceased 20-29 years previously. Use during the 1960s, 1970s, and 1980s was associated with similar proportional risk reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The incidence of mucinous tumours (12% of the total) seemed little affected by oral contraceptives, but otherwise the proportional risk reduction did not vary much between different histological types. In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1.2 to 0.8 per 100 users and mortality from 0.7 to 0.5 per 100; for every 5000 woman-years of use, about two ovarian cancers and one death from the disease before age 75 are prevented. Use of oral contraceptives confers long-term protection against ovarian cancer. These findings suggest that oral contraceptives have already prevented some 200,000 ovarian cancers and 100,000 deaths from the disease, and that over the next few decades the number of cancers prevented will rise to at least 30,000 per year.

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Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm.

Dennis S Chi, Eric L Eisenhauer, Oliver Zivanovic … (2009)

To determine the impact on progression-free survival (PFS) and overall survival (OS) of a programmatic change in surgical approach to advanced epithelial ovarian cancer. Two groups of patients with stage IIIC and IV ovarian, tubal, and peritoneal carcinoma were compared. Group 1, the control group, consisted of all 168 patients who underwent primary cytoreduction from 1/96 to 12/99. Group 2, the study group, consisted of all 210 patients who underwent primary surgery from 1/01 to 12/04, during which time a more comprehensive debulking of upper abdominal disease was utilized. There were no differences between the groups in age, primary site of disease, surgical stage, tumor grade, American Society of Anesthesiologists class, preoperative serum CA-125 and platelet levels, percentage with or amount of ascites, size or location of largest tumor mass, or type of postoperative chemotherapy. Patients in Group 2 vs Group 1 more frequently had extensive upper abdominal procedure(s) (38% vs 0%, respectively; P<0.001) and cytoreduction to residual disease <1 cm (80% vs 46%, respectively; P<0.01). Five-year PFS and OS rates were significantly improved in Group 2. For Group 2 vs Group 1 patients, 5-year PFS rates were 31% vs 14%, respectively (hazard ratio, 0.757; 95% CI, 0.601-0.953; P=0.01]; and 5-year OS rates were 47% vs 35%, respectively (HR, 0.764; 95% CI, 0.592-0.987; P=0.03]. The incorporation of extensive upper abdominal procedures resulted in increased optimal cytoreduction rates and significantly improved PFS and OS. A paradigm shift toward more complete primary cytoreduction can improve survival for patients with advanced ovarian, tubal, and peritoneal carcinomas.

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Author and article information

Journal

Journal ID (nlm-journal-id): 0365304

Journal ID (pubmed-jr-id): 3932

Journal ID (nlm-ta): Gynecol Oncol

Journal ID (iso-abbrev): Gynecol. Oncol.

Title: Gynecologic oncology

ISSN (Print): 0090-8258

ISSN (Electronic): 1095-6859

Publication date Nihms-submitted: 13 February 2015

Publication date (Electronic): 22 January 2015

Publication date (Print): April 2015

Publication date PMC-release: 01 April 2016

Volume: 137

Issue: 1

Pages: 77-85

Affiliations

[1 ]Department of Medical Oncology, Mayo Clinic, Rochester MN

[2 ]Department of Health Sciences Research, Mayo Clinic, Rochester MN

[3 ]Department of Obstetrics and of Gynecology, Mayo Clinic, Rochester MN

[4 ]Department of Anatomic Pathology, Mayo Clinic, Rochester MN

[5 ]Washington University, St. Louis, MO

Author notes

Corresponding Author: Matthew J. Maurer, Department of Health Sciences Research, Mayo Clinic, 200 1 ^ST ST SW, Rochester, MN 55905, Phone: 507.266.2064, Fax: 507.266.2478, maurer.matthew@ 123456mayo.edu

Article

Manuscript ID: NIHMS662821

DOI: 10.1016/j.ygyno.2015.01.539

PMC ID: 4380608

PubMed ID: 25620544

SO-VID: 2c0a8bcc-7a39-470f-b6b5-e5c106866883

License:

This manuscript version is made available under the CC BY-NC-ND 4.0 license.

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Assessment of published models and prognostic variables in epithelial ovarian cancer at Mayo Clinic

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Abstract

Objectives

Methods

Results

Conclusions

Related collections

Exponential Random Graph Models

Most cited references 17

Regression Modeling Strategies

Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls.

Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm.

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