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Expert Panel on GYN and OB Imaging, Venkatesan AM, Kilcoyne A, Akin EA, Chuang L, Hindman NM, Huang C, McCourt CK, Rauch GM, Sattari M, Schoenborn N, Schultz D, Sertic M, Small W, Stein EB, Suarez-Weiss K, Kang SK. ACR Appropriateness Criteria® Ovarian Cancer Screening: 2024 Update. J Am Coll Radiol 2025; 22:S359-S371. [PMID: 40409887 DOI: 10.1016/j.jacr.2025.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 05/25/2025]
Abstract
Ovarian cancer remains low in prevalence but has the highest mortality of all gynecologic malignancies. Population-based screening for ovarian cancer remains a topic of interest in contemporary practice, given that the majority of cancers encountered are high-grade aggressive malignancies, for which favorable survival is encountered in the setting of early-stage disease. This document summarizes a review of the available data from randomized and observational trials that have evaluated the role of imaging for ovarian cancer screening in average-risk and high-risk patients. When considering screening using pelvic ultrasound in average-risk patients, we found insufficient published evidence to recommend ovarian cancer screening. Randomized controlled trials have not demonstrated a mortality benefit in this setting. Screening with pelvic ultrasound may be appropriate for select patients at high risk, although the existing data remain limited as large, randomized trials have not been performed in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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Affiliation(s)
| | | | - Aoife Kilcoyne
- Panel Chair, Massachusetts General Hospital, Boston, Massachusetts
| | - Esma A Akin
- George Washington University Hospital, Washington, District of Columbia; Commission on Nuclear Medicine and Molecular Imaging
| | - Linus Chuang
- University of Vermont Larner College of Medicine Danbury Hospital, Burlington, Vermont; Society of Gynecologic Oncology
| | | | - Chenchan Huang
- New York University Langone Medical Center, New York, New York
| | - Carolyn Kay McCourt
- Washington University School of Medicine, Saint Louis, Missouri; American College of Obstetricians and Gynecologists
| | - Gaiane M Rauch
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Maryam Sattari
- University of Florida College of Medicine, Gainesville, Florida; Society of General Internal Medicine
| | - Nancy Schoenborn
- Johns Hopkins University School of Medicine, Baltimore, Maryland; American Geriatrics Society
| | - David Schultz
- Evansville Primary Care, Evansville, Indiana; American Academy of Family Physicians
| | - Madeleine Sertic
- Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - William Small
- Loyola University Chicago, Stritch School of Medicine, Department of Radiation Oncology, Cardinal Bernardin Cancer Center, Maywood, Illinois; Commission on Radiation Oncology
| | - Erica B Stein
- University of Michigan Medical Center, Ann Arbor, Michigan
| | | | - Stella K Kang
- Specialty Chair, New York University Medical Center, New York, New York
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Menon U, Gentry-Maharaj A, Burnell M, Ryan A, Kalsi JK, Singh N, Dawnay A, Fallowfield L, McGuire AJ, Campbell S, Skates SJ, Parmar M, Jacobs IJ. Mortality impact, risks, and benefits of general population screening for ovarian cancer: the UKCTOCS randomised controlled trial. Health Technol Assess 2025; 29:1-93. [PMID: 37183782 PMCID: PMC10542866 DOI: 10.3310/bhbr5832] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023] Open
Abstract
Background Ovarian and tubal cancers are lethal gynaecological cancers, with over 50% of the patients diagnosed at advanced stage. Trial design Randomised controlled trial involving 27 primary care trusts adjacent to 13 trial centres based at NHS Trusts in England, Wales and Northern Ireland. Methods Postmenopausal average-risk women, aged 50-74, with intact ovaries and no previous ovarian or current non-ovarian cancer. Interventions One of two annual screening strategies: (1) multimodal screening (MMS) using a longitudinal CA125 algorithm with repeat CA125 testing and transvaginal scan (TVS) as second line test (2) ultrasound screening (USS) using TVS alone with repeat scan to confirm any abnormality. The control (C) group had no screening. Follow-up was through linkage to national registries, postal follow-up questionnaires and direct communication with trial centres and participants. Objective To assess comprehensively risks and benefits of ovarian cancer screening in the general population. Outcome Primary outcome was death due to ovarian or tubal cancer as assigned by an independent outcomes review committee. Secondary outcomes included incidence and stage at diagnosis of ovarian and tubal cancer, compliance, performance characteristics, harms and cost-effectiveness of the two screening strategies and a bioresource for future research. Randomisation The trial management system confirmed eligibility and randomly allocated participants using computer-generated random numbers to MMS, USS and C groups in a 1:1:2 ratio. Blinding Investigators and participants were unblinded and outcomes review committee was masked to randomisation group. Analyses Primary analyses were by intention to screen, comparing separately MMS and USS with C using the Versatile test. Results 1,243,282 women were invited and 205,090 attended for recruitment between April 2001 and September 2005. Randomised 202,638 women: 50,640 MMS, 50,639 USS and 101,359 C group. Numbers analysed for primary outcome 202,562 (>99.9%): 50,625 (>99.9%) MMS, 50,623 (>99.9%) USS, and 101,314 (>99.9%) C group. Outcome Women in MMS and USS groups underwent 345,570 and 327,775 annual screens between randomisation and 31 December 2011. At median follow-up of 16.3 (IQR 15.1-17.3) years, 2055 women developed ovarian or tubal cancer: 522 (1.0% of 50,625) MMS, 517 (1.0% of 50,623) USS, and 1016 (1.0% of 101314) in C group. Compared to the C group, in the MMS group, the incidence of Stage I/II disease was 39.2% (95% CI 16.1 to 66.9) higher and stage III/IV 10.2% (95% CI -21.3 to 2.4) lower. There was no difference in stage in the USS group. 1206 women died of the disease: 296 (0.6%) MMS, 291 (0.6%) USS, and 619 (0.6%) C group. There was no significant reduction in ovarian and tubal cancer deaths in either MMS (p = 0.580) or USS (p = 0.360) groups compared to the C group. Overall compliance with annual screening episode was 80.8% (345,570/420,047) in the MMS and 78.0% (327,775/420,047) in the USS group. For ovarian and tubal cancers diagnosed within one year of the last test in a screening episode, in the MMS group, the sensitivity, specificity and positive predictive values were 83.8% (95% CI 78.7 to 88.1), 99.8% (95% CI 99.8 to 99.9), and 28.8% (95% CI 25.5 to 32.2) and in the USS group, 72.2% (95% CI 65.9 to 78.0), 99.5% (95% CI 99.5 to 99.5), and 9.1% (95% CI 7.8 to 10.5) respectively. The final within-trial cost-effectiveness analysis was not undertaken as there was no mortality reduction. A bioresource (UKCTOCS Longitudinal Women's Cohort) of longitudinal outcome data and over 0.5 million serum samples including serial annual samples in women in the MMS group was established and to date has been used in many new studies, mainly focused on early detection of cancer. Harms Both screening tests (venepuncture and TVS) were associated with minor complications with low (8.6/100,000 screens MMS; 18.6/100,000 screens USS) complication rates. Screening itself did not cause anxiety unless more intense repeat testing was required following abnormal screens. In the MMS group, for each screen-detected ovarian or tubal cancer, an additional 2.3 (489 false positives; 212 cancers) women in the MMS group had unnecessary false-positive (benign adnexal pathology or normal adnexa) surgery. Overall, 14 (489/345,572 annual screens) underwent unnecessary surgery per 10,000 screens. In the USS group, for each screen-detected ovarian or tubal cancer, an additional 10 (1630 false positives; 164 cancers) underwent unnecessary false-positive surgery. Overall, 50 (1630/327,775 annual screens) women underwent unnecessary surgery per 10,000 screens. Conclusions Population screening for ovarian and tubal cancer for average-risk women using these strategies should not be undertaken. Decreased incidence of Stage III/IV cancers during multimodal screening did not translate to mortality reduction. Researchers should be cautious about using early stage as a surrogate outcome in screening trials. Meanwhile the bioresource provides a unique opportunity to evaluate early cancer detection tests. Funding Long-term follow-up UKCTOCS (2015-2020) - National Institute for Health and Care Research (NIHR HTA grant 16/46/01), Cancer Research UK, and The Eve Appeal. UKCTOCS (2001-2014) - Medical Research Council (MRC) (G9901012/G0801228), Cancer Research UK (C1479/A2884), and the UK Department of Health, with additional support from The Eve Appeal. Researchers at UCL were supported by the NIHR UCL Hospitals Biomedical Research Centre and by MRC Clinical Trials Unit at UCL core funding (MR_UU_12023).
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Affiliation(s)
- Usha Menon
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Matthew Burnell
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Andy Ryan
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Jatinderpal K Kalsi
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
- CRUK UCL Centre, UCL Cancer Institute, London, UK
| | - Naveena Singh
- Department of Cellular Pathology, Barts Health NHS Trust, London, UK
| | - Anne Dawnay
- Department of Clinical Biochemistry, Barts Health NHS Service Trust, London, UK
| | - Lesley Fallowfield
- Sussex Health Outcomes Research and Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Brighton, UK
| | | | | | - Steven J Skates
- Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Mahesh Parmar
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Ian J Jacobs
- Department of Women's Health, University of New South Wales, Sydney, NSW, Australia
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Duan H, Liu X, Zhang Y, Liu Y, Ji Y, Zhang Y, Fan Z, Liu S, Yang L, Xu T, Tian J, Li W, Lyu Z, Song F, Song F, Huang Y. Risk-stratified CA125 screening integrating CA125 trajectories, trajectory-specific progression and transvaginal ultrasound for ovarian cancer. J Ovarian Res 2024; 17:210. [PMID: 39462415 PMCID: PMC11514894 DOI: 10.1186/s13048-024-01535-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 10/09/2024] [Indexed: 10/29/2024] Open
Abstract
BACKGROUNDS Cancer antigen 125 (CA125) is widely used for screening ovarian cancer (OC), yet its effectiveness remains debated. Potential factors may include ineffective cut-off value for CA125 in screening, as well as a lack of consideration for CA125 trajectories and trajectory-specific progression. METHODS Based on data from multiple rounds of CA125 tests and transvaginal ultrasound (TVU) examinations conducted on 28,456 women in the PLCO Trial, time-dependent receiver-operating-characteristic curves (ROCs) and area-under-the-curves (tdAUCs) analyses were employed to identify the optimal CA125 cut-off values for OC screening. Participants were categorized into four CA125 trajectories: stable negative CA125 (CA125SN), loss of positive CA125 (CA125LP), stable positive CA125 (CA125SP), and gain of positive CA125 (CA125GP). The associations between different CA125 trajectories, trajectory-specific progression indicators, and OC risk were explored. The effectiveness of risk-stratified CA125 screening, incorporating CA125 trajectories, trajectory-specific progression, and TVU, was evaluated using hazard ratio and 95% confidence intervals [HR (95%CIs)], with adjustments for potential confounders. RESULTS After a median follow-up of 14.8 years for OC incidence and 23.8 years for OC mortality, 250 OC cases and 218 OC deaths were identified. The tdAUC for 10-year OC incidence with CA125 was 0.663, with an optimal cut-off value of 13.00 U/ml. Trajectory analyses showed that both CA125SP and CA125GP were significantly associated with increased risks of OC incidence [HRs (95%CIs): 2.00(1.47-2.73) and 3.06(2.25-4.16)] and mortality [HRs (95%CIs):1.58(1.13-2.21) and 2.60(1.87-3.62)] compared to CA125SN. Trajectory-specific progression analyses identified relative velocity as the optimal progression indicators for both CA125SP and CA125GP (tdAUCs: 0.712 and 0.767), with optimal cut-off values of 9% and 32% per year, respectively. Positive progression was associated with significantly increased risks of OC incidence [HRs (95%CI): 7.26(4.00-13.17) and 3.83(1.96-7.51) CA125GP and CA125SP] and mortality [HRs (95%CI): 8.03(4.15-15.56) and 6.04(2.78-13.14)] compared to negative progression. Optimized risk-stratified CA125 screening, which integrated CA125 trajectories, trajectory-specific progression, and TVU, reduced missed OC by 3.6% and improved accuracy compared to traditional screening methods. CONCLUSIONS Incorporating CA125 trajectories and trajectory-specific progression into screening protocols enhances the identification of the population at high-risk of OC. An optimized screening strategy, which includes these factors along with TVU, is recommended to improve the effectiveness of OC screening.
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Affiliation(s)
- Hongyuan Duan
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Xiaomin Liu
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Yu Zhang
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Ya Liu
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Yuting Ji
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Yunmeng Zhang
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Zeyu Fan
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Siwen Liu
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Lei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Tingting Xu
- Department of International Affairs, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, China
| | - Jing Tian
- Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, China
| | - Weiqin Li
- Project Office, Tianjin Women and Children's Health Center, Tianjin, 300070, China
| | - Zhangyan Lyu
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Fangfang Song
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Fengju Song
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China
| | - Yubei Huang
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, Tianjin, 300060, China.
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Burke W, Barkley J, Barrows E, Brooks R, Gecsi K, Huber-Keener K, Jeudy M, Mei S, O'Hara JS, Chelmow D. Executive Summary of the Ovarian Cancer Evidence Review Conference. Obstet Gynecol 2023; 142:179-195. [PMID: 37348094 PMCID: PMC10278568 DOI: 10.1097/aog.0000000000005211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/29/2022] [Accepted: 01/19/2023] [Indexed: 06/24/2023]
Abstract
The Centers for Disease Control and Prevention awarded funding to the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines as a first step toward developing evidence-based educational materials for women's health care clinicians about ovarian cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at a virtual meeting of stakeholder professional and patient advocacy organizations in February 2022. This article is the executive summary of the relevant literature and existing recommendations to guide clinicians in the prevention, early diagnosis, and special considerations of ovarian cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.
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Affiliation(s)
- William Burke
- Departments of Obstetrics and Gynecology, Stony Brook University Hospital, New York, New York, Creighton University School of Medicine, Phoenix, Arizona, Virginia Commonwealth University School of Medicine, Richmond, Virginia, the University of California, Davis, Davis, California, the Medical College of Wisconsin, Milwaukee, Wisconsin, the University of Iowa Hospitals and Clinics, Iowa City, Iowa, and New York University Langone School of Medicine, New York; and the American College of Obstetricians and Gynecologists, Washington, DC
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Nigam A, Xu B, Spanheimer PM, Ganly I, Tuttle RM, Wong RJ, Shaha AR, Ghossein RA, Untch BR. Tumor Grade Predicts for Calcitonin Doubling Times and Disease-Specific Outcomes After Resection of Medullary Thyroid Carcinoma. Thyroid 2022; 32:1193-1200. [PMID: 35950622 PMCID: PMC9595606 DOI: 10.1089/thy.2022.0217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Background: Tumor grade is a new validated prognostic factor for medullary thyroid cancer (MTC). Calcitonin doubling time can predict MTC recurrence. We aimed to describe the association of tumor grade with calcitonin doubling and its effect on disease-specific outcomes times after resection. Methods: A retrospective analysis of MTC patients who underwent resection at a single tertiary-care cancer center between 1986 and 2017 were evaluated. Tumors were designated as high-grade MTC if two head and neck pathologists identified mitotic index ≥5 per 2 mm2, tumor necrosis, or a Ki67 proliferative index ≥5% within the tumor. Calcitonin doubling time was calculated using a validated calculator with at least three consecutive levels. Using Cox proportional hazards models, outcomes evaluated included locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Results: Among 117 patients, 95 were low grade and 22 high grade. Median follow-up was 70.2 months. High-grade patients demonstrated significantly faster calcitonin doubling times when compared with low-grade patients (8.51 ± 3.22 months vs. 38.42 ± 11.19 months; p < 0.001). In addition, most high-grade patients (66.7%) had calcitonin doubling times less than 1 year compared with fewer low-grade patients (1.0%; p < 0.001). High- and low-grade patients were further stratified by those who had calcitonin doubling times less than or greater than 2 years-a previously validated prognostic cutoff point. For patients with calcitonin doubling times less than 2 years, 70% were high grade, while 30% were low grade (p < 0.001). On multivariate analysis comparing grade and calcitonin doubling times, high-grade patients had significantly worse LRFS (hazards ratio [HR] 4.77 [confidence interval; CI 1.19-8.81]), DMFS (HR 7.25 [CI 2.36-22.28]), and OS (HR 6.04 [CI 1.85-19.72]; p < 0.05 for all), while calcitonin doubling times less than 2 years had worse DMFS (HR 7.22 [CI 1.05-49.75]). High-grade patients with calcitonin doubling times less than 2 years had associated worse LRFS and OS (both p < 0.05) compared with low-grade patients. Conclusions: The majority of high-grade MTC patients have calcitonin doubling times less than 2years. Close monitoring should be advocated for patients assessed to have high-grade tumors as they are at risk for poor disease-specific outcomes and structural recurrence.
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Affiliation(s)
- Aradhya Nigam
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Bin Xu
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Philip M. Spanheimer
- Department of Surgery and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Ian Ganly
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - R. Michael Tuttle
- Department of Endocrinology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Richard J. Wong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Ashok R. Shaha
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Ronald A. Ghossein
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Brian R. Untch
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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Tayob N, Feng Z. Personalized statistical learning algorithms to improve the early detection of cancer using longitudinal biomarkers. Cancer Biomark 2022; 33:199-210. [PMID: 35213362 DOI: 10.3233/cbm-210307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Patients undergoing screening for early detection of cancer have serial biomarker measurements that are not traditionally being incorporated into decision making when evaluating biomarkers. OBJECTIVE We discuss statistical learning algorithms that have the ability to learn from patient history to make personalized decision rules to improve the early detection of cancer. These artificial intelligence algorithms are able to learn in real time from data collected on the patient to identify changes in the patient that could signal asymptomatic cancer. METHODS We discuss the parametric empirical Bayes (PEB) algorithm for a single biomarker and a Bayesian screening algorithm for multiple biomarkers. RESULTS We provide tools to implement these algorithms and discuss their clinical utility for the early detection of hepatocellular carcinoma (HCC). The PEB algorithm is a robust, easily implemented algorithm for defining patient specific thresholds that can improve the patient-level sensitivity of a biomarker in many settings, including HCC. The fully Bayesian algorithm, while more complex, can accommodate multiple biomarkers and further improve the clinical utility of the algorithms. CONCLUSIONS These algorithms could be used in many clinical settings and we aim to guide the reader on how these algorithms may improve the detection performance of their biomarkers.
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Affiliation(s)
- Nabihah Tayob
- Department of Data Science, Dana Farber Cancer Institute, Boston, MA, USA.,Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Ziding Feng
- Biostatistics Program, Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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OSov: An Interactive Web Server to Evaluate Prognostic Biomarkers for Ovarian Cancer. BIOLOGY 2021; 11:biology11010023. [PMID: 35053021 PMCID: PMC8773055 DOI: 10.3390/biology11010023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 11/16/2022]
Abstract
Simple Summary The OSov web server incorporates gene expression profiles with clinical risk factors to estimate the ovarian cancers patients’ survival, and provides a tool for multiple analysis, such as forest-plot, uni/multi-variate survival analysis, Kaplan-Meier plot and nomogram construction. Abstract Ovarian cancer is one of the most aggressive and highly lethal gynecological cancers. The purpose of our study is to build a free prognostic web server to help researchers discover potential prognostic biomarkers by integrating gene expression profiling data and clinical follow-up information of ovarian cancer. We construct a prognostic web server OSov (Online consensus Survival analysis for Ovarian cancer) based on RNA expression profiles. OSov is a user-friendly web server which could present a Kaplan–Meier plot, forest plot, nomogram and survival summary table of queried genes in each individual cohort to evaluate the prognostic potency of each queried gene. To assess the performance of OSov web server, 163 previously published prognostic biomarkers of ovarian cancer were tested and 72% of them had their prognostic values confirmed in OSov. It is a free and valuable prognostic web server to screen and assess survival-associated biomarkers for ovarian cancer.
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Menon U, Gentry-Maharaj A, Burnell M, Singh N, Ryan A, Karpinskyj C, Carlino G, Taylor J, Massingham SK, Raikou M, Kalsi JK, Woolas R, Manchanda R, Arora R, Casey L, Dawnay A, Dobbs S, Leeson S, Mould T, Seif MW, Sharma A, Williamson K, Liu Y, Fallowfield L, McGuire AJ, Campbell S, Skates SJ, Jacobs IJ, Parmar M. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet 2021; 397:2182-2193. [PMID: 33991479 PMCID: PMC8192829 DOI: 10.1016/s0140-6736(21)00731-5] [Citation(s) in RCA: 396] [Impact Index Per Article: 99.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 03/22/2021] [Accepted: 03/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS. METHODS In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032. FINDINGS Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group. INTERPRETATION The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended. FUNDING National Institute for Health Research, Cancer Research UK, and The Eve Appeal.
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Affiliation(s)
- Usha Menon
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
| | - Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Matthew Burnell
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Naveena Singh
- Department of Cellular Pathology, Barts Health NHS Trust, London, UK
| | - Andy Ryan
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Chloe Karpinskyj
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Giulia Carlino
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Julie Taylor
- Clinical Epidemiology, Institute of Health Informatics, University College London, London, UK
| | - Susan K Massingham
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Maria Raikou
- Department of Health Policy, London School of Economics and Political Science, London, UK; Department of Economics, University of Piraeus, Athens, Greece
| | - Jatinderpal K Kalsi
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Robert Woolas
- Department of Gynaecological Oncology, Queen Alexandra Hospital, Portsmouth, UK
| | - Ranjit Manchanda
- Department of Gynaecological Oncology, Barts Health NHS Trust, London, UK; Wolfson Institute of Preventive Medicine, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
| | - Rupali Arora
- Department of Cellular Pathology, University College London Hospitals NHS Trust, London, UK
| | - Laura Casey
- Department of Cellular Pathology, Barts Health NHS Trust, London, UK
| | - Anne Dawnay
- Department of Clinical Biochemistry, Barts Health NHS Trust, London, UK
| | - Stephen Dobbs
- Department of Gynaecological Oncology, Belfast City Hospital, Belfast, UK
| | - Simon Leeson
- Department of Obstetrics and Gynaecology, Ysbyty Gwynedd, Bangor, UK
| | - Tim Mould
- Department of Gynaecological Oncology, University College London Hospitals NHS Trust, London, UK
| | - Mourad W Seif
- Division of Gynaecology and Cancer Sciences, St Mary's Hospital, Manchester, UK
| | - Aarti Sharma
- Department of Obstetrics and Gynaecology, University Hospital of Wales, Cardiff, UK
| | - Karin Williamson
- Department of Gynaecological Oncology, Nottingham City Hospital, Nottingham, UK
| | - Yiling Liu
- MGH Biostatistics, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Lesley Fallowfield
- Sussex Health Outcomes Research and Education in Cancer, SHORE-C, Brighton and Sussex Medical School, University of Sussex, Brighton, UK
| | - Alistair J McGuire
- Department of Health Policy, London School of Economics and Political Science, London, UK
| | | | - Steven J Skates
- MGH Biostatistics, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Ian J Jacobs
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Department of Women's Health, University of New South Wales, Sydney, NSW, Australia
| | - Mahesh Parmar
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
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9
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An Update on Screening and Prevention for Breast and Gynecological Cancers in Average and High Risk Individuals. Am J Med Sci 2020; 360:489-510. [DOI: 10.1016/j.amjms.2020.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 05/22/2020] [Accepted: 06/03/2020] [Indexed: 11/21/2022]
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10
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Lentz SE, Powell CB, Haque R, Armstrong MA, Anderson M, Liu Y, Jiang W, Chillemi G, Shaw S, Alvarado MM, Kushi LH, Skates SJ. Development of a longitudinal two-biomarker algorithm for early detection of ovarian cancer in women with BRCA mutations. Gynecol Oncol 2020; 159:804-810. [PMID: 33012551 DOI: 10.1016/j.ygyno.2020.09.021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 09/12/2020] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. METHODS Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. RESULTS A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). CONCLUSION A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.
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Affiliation(s)
- Scott E Lentz
- Kaiser Permanente Southern California, Research & Evaluation, Pasadena, CA, United States of America
| | - C Bethan Powell
- Division of Research, Kaiser Permanente, Northern California, Oakland, CA, United States of America; Kaiser Permanente Northern California Gynecologic Oncology Program, Oakland, CA, United States of America.
| | - Reina Haque
- Kaiser Permanente Southern California, Research & Evaluation, Pasadena, CA, United States of America; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, United States of America
| | - Mary Anne Armstrong
- Division of Research, Kaiser Permanente, Northern California, Oakland, CA, United States of America
| | - Meredith Anderson
- Division of Research, Kaiser Permanente, Northern California, Oakland, CA, United States of America
| | - Yiling Liu
- Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States of America
| | - Wenqing Jiang
- Division of Research, Kaiser Permanente, Northern California, Oakland, CA, United States of America
| | - Giulia Chillemi
- Division of Research, Kaiser Permanente, Northern California, Oakland, CA, United States of America
| | - Sally Shaw
- Kaiser Permanente Southern California, Research & Evaluation, Pasadena, CA, United States of America
| | - Monica M Alvarado
- Kaiser Permanente Southern California, Research & Evaluation, Pasadena, CA, United States of America
| | - Lawrence H Kushi
- Division of Research, Kaiser Permanente, Northern California, Oakland, CA, United States of America
| | - Steven J Skates
- Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States of America
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11
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Han Y, Albert PS, Berg CD, Wentzensen N, Katki HA, Liu D. Statistical approaches using longitudinal biomarkers for disease early detection: A comparison of methodologies. Stat Med 2020; 39:4405-4420. [PMID: 32939802 PMCID: PMC10086614 DOI: 10.1002/sim.8731] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 03/25/2020] [Accepted: 07/24/2020] [Indexed: 11/06/2022]
Abstract
Early detection of clinical outcomes such as cancer may be predicted using longitudinal biomarker measurements. Tracking longitudinal biomarkers as a way to identify early disease onset may help to reduce mortality from diseases like ovarian cancer that are more treatable if detected early. Two disease risk prediction frameworks, the shared random effects model (SREM) and the pattern mixture model (PMM) could be used to assess longitudinal biomarkers on disease early detection. In this article, we studied the discrimination and calibration performances of SREM and PMM on disease early detection through an application to ovarian cancer, where early detection using the risk of ovarian cancer algorithm (ROCA) has been evaluated. Comparisons of the above three approaches were performed via analyses of the ovarian cancer data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Discrimination was evaluated by the time-dependent receiver operating characteristic curve and its area, while calibration was assessed using calibration plot and the ratio of observed to expected number of diseased subjects. The out-of-sample performances were calculated via using leave-one-out cross-validation, aiming to minimize potential model overfitting. A careful analysis of using the biomarker cancer antigen 125 for ovarian cancer early detection showed significantly improved discrimination performance of PMM as compared with SREM and ROCA, nevertheless all approaches were generally well calibrated. Robustness of all approaches was further investigated in extensive simulation studies. The improved performance of PMM relative to ROCA is in part due to the fact that the biomarker measurements were taken at a yearly interval, which is not frequent enough to reliably estimate the changepoint or the slope after changepoint in cases under ROCA.
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Affiliation(s)
- Yongli Han
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Paul S Albert
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Christine D Berg
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Nicolas Wentzensen
- Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Hormuzd A Katki
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Danping Liu
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
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12
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Gentry-Maharaj A, Blyuss O, Ryan A, Burnell M, Karpinskyj C, Gunu R, Kalsi JK, Dawnay A, Marino IP, Manchanda R, Lu K, Yang WL, Timms JF, Parmar M, Skates SJ, Bast RC, Jacobs IJ, Zaikin A, Menon U. Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women. Cancers (Basel) 2020; 12:E1931. [PMID: 32708856 PMCID: PMC7409061 DOI: 10.3390/cancers12071931] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/07/2020] [Accepted: 07/14/2020] [Indexed: 12/11/2022] Open
Abstract
Longitudinal CA125 algorithms are the current basis of ovarian cancer screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-ovarian cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-ovarian cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2-5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871-0.952) and 90.5% (82.5-98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in ovarian cancer screening of postmenopausal women.
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Affiliation(s)
- Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (C.K.); (R.M.); (M.P.)
| | - Oleg Blyuss
- School of Physics, Astronomy and Mathematics, University of Hertfordshire, Hatfield AL10 9AB, UK;
- Department of Paediatrics and Paediatric Infectious Diseases, Sechenov First Moscow State Medical University, Moscow 119991, Russia;
| | - Andy Ryan
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (C.K.); (R.M.); (M.P.)
| | - Matthew Burnell
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (C.K.); (R.M.); (M.P.)
| | - Chloe Karpinskyj
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (C.K.); (R.M.); (M.P.)
| | - Richard Gunu
- Department of Women’s Cancer, Institute for Women’s Health, University College London, London WC1E 6BT, UK; (R.G.); (J.K.K.); (J.F.T.); (I.J.J.)
| | - Jatinderpal K. Kalsi
- Department of Women’s Cancer, Institute for Women’s Health, University College London, London WC1E 6BT, UK; (R.G.); (J.K.K.); (J.F.T.); (I.J.J.)
| | - Anne Dawnay
- Clinical Biochemistry, Barts Health NHS Trust, London E1 8PR, UK;
| | - Ines P. Marino
- Department of Biology and Geology, Physics and Inorganic Chemistry, Universidad Rey Juan Carlos, 28933 Madrid, Spain;
| | - Ranjit Manchanda
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (C.K.); (R.M.); (M.P.)
- Wolfson Institute of Preventive Medicine, Barts CRUK Cancer Centre, Queen Mary University of London, London EC1M 6BQ, UK
- Department of Gynaecological Oncology, St Bartholomew’s Hospital, Barts Health NHS Trust, London EC1A 7BE, UK
| | - Karen Lu
- University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; (K.L.); (W.-L.Y.); (R.C.B.J.)
| | - Wei-Lei Yang
- University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; (K.L.); (W.-L.Y.); (R.C.B.J.)
| | - John F. Timms
- Department of Women’s Cancer, Institute for Women’s Health, University College London, London WC1E 6BT, UK; (R.G.); (J.K.K.); (J.F.T.); (I.J.J.)
| | - Mahesh Parmar
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (C.K.); (R.M.); (M.P.)
| | - Steven J. Skates
- Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;
| | - Robert C. Bast
- University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; (K.L.); (W.-L.Y.); (R.C.B.J.)
| | - Ian J. Jacobs
- Department of Women’s Cancer, Institute for Women’s Health, University College London, London WC1E 6BT, UK; (R.G.); (J.K.K.); (J.F.T.); (I.J.J.)
- University of New South Wales, Sydney 2052, Australia
| | - Alexey Zaikin
- Department of Paediatrics and Paediatric Infectious Diseases, Sechenov First Moscow State Medical University, Moscow 119991, Russia;
- Department of Women’s Cancer, Institute for Women’s Health, University College London, London WC1E 6BT, UK; (R.G.); (J.K.K.); (J.F.T.); (I.J.J.)
- Department of Applied Mathematics, Lobachevsky University of Nyzhniy Novgorod, Nizhniy Novgorod 603105, Russia
- Department of Mathematics, University College London, London WC1H 0AY, UK
| | - Usha Menon
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (C.K.); (R.M.); (M.P.)
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13
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Garcia C, Sullivan MW, Lothamer H, Harrison KM, Chatfield L, Thomas MH, Modesitt SC. Mechanisms to increase cascade testing in hereditary breast and ovarian cancer: Impact of introducing standardized communication aids into genetic counseling. J Obstet Gynaecol Res 2020; 46:1835-1841. [PMID: 32656916 DOI: 10.1111/jog.14366] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/02/2020] [Accepted: 06/07/2020] [Indexed: 11/30/2022]
Abstract
AIM Precancer identification of women with hereditary breast and ovarian cancer (HBOC) could prevent 20% of these ovarian cancers. The objective was to determine whether standardized Facing Our Risk of Cancer Empowered (FORCE) materials are acceptable, improve knowledge of HBOC and increase disclosure to family members. METHODS A prospective cohort of women with breast or ovarian cancer was identified prior to genetic testing. Subjects completed a baseline knowledge survey and were provided three communication aids. Knowledge, acceptability and communication to family members were reassessed at 6 months and compared to a retrospective cohort who had undergone genetic testing for breast or ovarian cancer prior to the intervention. The primary outcome was increase in HBOC knowledge, requiring 20 pre- and postknowledge scores to detect a 10% difference. RESULTS Forty women were enrolled. The median age at cancer diagnosis was 50 years and 55% had a family history of breast or ovarian cancer. Though subjects found the resources acceptable, knowledge scores did not improve after their use. Disclosure rates were of no different between cohorts (83% preintervention vs 77% postintervention, P = 0.26) though there was an increase in deleterious mutation carriers, 0% (0/6) preintervention vs 100% (22/22) postintervention. Rates of subsequent testing in relatives were low in both preintervention and postintervention cohorts (0% vs 4.5%). CONCLUSION Inclusion of standardized communication tools is acceptable to patients. Knowledge did not improve after their use. In deleterious mutation carriers, disclosure rates increased postintervention.
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Affiliation(s)
- Christine Garcia
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia, Charlottesville, Virginia, USA.,Kaiser San Francisco, 2238 Geary Blvd, San Francisco, CA, 94114, 415-833-4199, USA
| | - Mackenzie W Sullivan
- Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Heather Lothamer
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia, Charlottesville, Virginia, USA
| | - Kara M Harrison
- Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Lindsay Chatfield
- Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Martha H Thomas
- Cancer Genetics, Emily Couric Cancer Center, University of Virginia, Charlottesville, Virginia, USA
| | - Susan C Modesitt
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia, Charlottesville, Virginia, USA
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14
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The reduction of CA 125 serum levels in BRCA 1/2 mutation carriers after risk-reducing salpingo-oophorectomy is only partially associated with surgery: a prospective cohort, other biomarker controlled, study. Eur J Cancer Prev 2020; 29:350-356. [DOI: 10.1097/cej.0000000000000606] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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15
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Ovarian cancer screening: Current status and future directions. Best Pract Res Clin Obstet Gynaecol 2020; 65:32-45. [PMID: 32273169 DOI: 10.1016/j.bpobgyn.2020.02.010] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 02/26/2020] [Accepted: 02/26/2020] [Indexed: 02/08/2023]
Abstract
Ovarian cancer is the third most common gynaecological malignancy and the most lethal worldwide. Most patients are diagnosed with advanced disease which carries significant mortality. Improvements in treatment have only resulted in modest increases in survival. This has driven efforts to reduce mortality through screening. Multimodal ovarian cancer screening using a longitudinal CA125 algorithm has resulted in diagnosis at an earlier stage, both in average and high risk women in two large UK trials. However, no randomised controlled trial has demonstrated a definitive mortality benefit. Extended follow up is underway in the largest trial to date, UKCTOCS, to explore the delayed reduction in mortality that was noted. Meanwhile, screening is not currently recommended in the general population Some countries offer surveillance of high risk women. Novel screening modalities and longitudinal biomarker algorithms offer potential improvements to future screening strategies as does the development of better risk stratification tools.
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Bullock RG, Smith A, Munroe DG, Ueland FR, Goodrich ST, Pappas TC, Fredericks TI, Bonato V. Combining A Second-Generation Multivariate Index Assay with Ovarian Imaging Improves the Preoperative Assessment of An Adnexal Mass. J Surg Oncol 2019. [DOI: 10.31487/j.jso.2019.03.04] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Background: To understand the relationship between imaging and the next generation multivariate index assay (MIA2G) in the preoperative assessment of an adnexal mass. Methods: Serum samples and imaging data from two previously published studies are reanalyzed using the MIA2G test. We calculated the clinical performance of MIA2G and discrete imaging features associated with malignant risk. Results: 878 women were eligible for this analysis, 48.3% post-menopausal and 51.7% pre-menopausal. The prevalence of having a malignant pathology was 18%. Ultrasound was the most frequently used imaging modality. The combination of MIA2G “or” ultrasound resulted in higher sensitivity than either test alone, 93.5% compared to 87.6% for MIA2G and 74.2% for ultrasound. The negative predictive value was high: 94.6% for ultrasound, 98.1% for MIA2G “or” ultrasound. MIA2G “and” ultrasound had higher specificity but lower sensitivity than MIA2G or ultrasound alone. Similar results were seen for CT scan when evaluated with MIA2G. Conclusion: MIA2G and pelvic imaging are complementary tests and interpreting them together can provide important information about the malignant risk of an ovarian tumor. For physicians making decisions about a referral to a specialist, the combination of MIA2G “or” ultrasound has the highest sensitivity in predicting ovarian malignancy.
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17
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A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells. Cancers (Basel) 2019; 11:cancers11050655. [PMID: 31083587 PMCID: PMC6563002 DOI: 10.3390/cancers11050655] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/02/2019] [Accepted: 05/08/2019] [Indexed: 02/07/2023] Open
Abstract
Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.
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18
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Carvalho VPD, Grassi ML, Palma CDS, Carrara HHA, Faça VM, Candido Dos Reis FJ, Poersch A. The contribution and perspectives of proteomics to uncover ovarian cancer tumor markers. Transl Res 2019; 206:71-90. [PMID: 30529050 DOI: 10.1016/j.trsl.2018.11.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 11/07/2018] [Accepted: 11/13/2018] [Indexed: 12/13/2022]
Abstract
Despite all the advances in understanding the mechanisms involved in ovarian cancer (OC) development, many aspects still need to be unraveled and understood. Tumor markers (TMs) are of special interest in this disease. Some aspects of clinical management of OC might be improved by the use of validated TMs, such as differentiating subtypes, defining the most appropriate treatment, monitoring the course of the disease, or predicting clinical outcome. The Food and Drug Administration (FDA) has approved a few TMs for OC: CA125 (cancer antigen 125; monitoring), HE4 (Human epididymis protein; monitoring), ROMA (Risk Of Malignancy Algorithm; HE4+CA125; prediction of malignancy) and OVA1 (Vermillion's first-generation Multivariate Index Assay [MIA]; prediction of malignancy). Proteomics can help advance the research in the field of TMs for OC. A variety of biological materials are being used in proteomic analysis, among them tumor tissues, interstitial fluids, tumor fluids, ascites, plasma, and ovarian cancer cell lines. However, the discovery and validation of new TMs for OC is still very challenging. The enormous heterogeneity of histological types of samples and the individual variability of patients (lifestyle, comorbidities, drug use, and family history) are difficult to overcome in research protocols. In this work, we sought to gather relevant information regarding TMs, OC, biological samples for proteomic analysis, as well as markers and algorithms approved by the FDA for use in clinical routine.
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Affiliation(s)
| | - Mariana Lopes Grassi
- Department of Biochemistry and Immunology, FMRP, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | - Camila de Souza Palma
- Department of Biochemistry and Immunology, FMRP, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | | | - Vitor Marcel Faça
- Department of Biochemistry and Immunology, FMRP, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | | | - Aline Poersch
- Department of Biochemistry and Immunology, FMRP, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil.
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19
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Mubarak AI, Morani AC, Samuel J, Sun J, Wei W, Bhosale P. Can Presurgical Ultrasound Predict Survival in Women With Ovarian Masses? Ultrasound Q 2019; 35:39-44. [PMID: 30516730 PMCID: PMC11864591 DOI: 10.1097/ruq.0000000000000401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE This study aimed to determine the ability of ultrasound to predict survival and detect more aggressive tumors in women with ovarian masses. MATERIALS AND METHODS Institutional review board approval was obtained. A total of 167 patients who presented with adnexal mass/masses were included. These were documented as benign or malignant on ultrasound. Age, date of diagnosis and date of death, type of tumor, and tumor marker cancer antigen 125 (CA-125) values were recorded. A CA-125 value of less than 35 U/mL was considered normal. All cases underwent surgery. Pathologic findings were considered as reference standard. The 2 × 2 cross-tabulations were used to correlate dichotomized CA-125, US diagnosis (benign vs malignant), and pathologic status. Difference of distributions was tested using the Wilcoxon rank sum test, and their association was tested using the Fisher exact test. All tests were 2-sided, and P values of 0.05 or less were considered statistically significant. Kaplan-Meir curves were generated to estimate survival. RESULTS There was a statistically significant difference in patients with benign versus malignant tumors based on pathology (P < 0.0001) and ultrasound (P < 0.0003). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ultrasound were 55%, 86%, 90% and 46%, and 81%. Patients diagnosed as having malignant tumors based on ultrasound had statistically significant worse overall survival. Probability of survival based on pathologic diagnosis of malignancy was statistically significant at P < 0.0003; based on ultrasound, P < 0.0001; and based on CA-125, P < 0.041. CONCLUSION Patients who had ultrasound-based prediction of ovarian malignancy had overall worse survival probability (P < 0.0001) compared with CA-125- or pathology-based prediction.
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Affiliation(s)
- Ahmad Iyad Mubarak
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ajaykumar C Morani
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jessica Samuel
- University of California at Los Angeles, Los Angeles, CA, United States
| | - Jia Sun
- Department of Biotatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wei Wei
- Department of Biotatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Priya Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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20
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Berek JS, Kehoe ST, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet 2018; 143 Suppl 2:59-78. [PMID: 30306591 DOI: 10.1002/ijgo.12614] [Citation(s) in RCA: 197] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The Gynecologic Oncology Committee of FIGO in 2014 revised the staging of ovarian cancer, incorporating ovarian, fallopian tube, and peritoneal cancer into the same system. Most of these malignancies are high-grade serous carcinomas (HGSC). Stage IC is now divided into three categories: IC1 (surgical spill); IC2 (capsule ruptured before surgery or tumor on ovarian or fallopian tube surface); and IC3 (malignant cells in the ascites or peritoneal washings). The updated staging includes a revision of Stage IIIC based on spread to the retroperitoneal lymph nodes alone without intraperitoneal dissemination. This category is now subdivided into IIIA1(i) (metastasis ≤10 mm in greatest dimension), and IIIA1(ii) (metastasis >10 mm in greatest dimension). Stage IIIA2 is now "microscopic extrapelvic peritoneal involvement with or without positive retroperitoneal lymph node" metastasis. This review summarizes the genetics, surgical management, chemotherapy, and targeted therapies for epithelial cancers, and the treatment of ovarian germ cell and stromal malignancies.
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Affiliation(s)
- Jonathan S Berek
- Stanford Women's Cancer Center, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
| | - Sean T Kehoe
- Institute of Cancer and Genomics, University of Birmingham, Birmingham, UK
| | - Lalit Kumar
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Michael Friedlander
- Royal Hospital for Women, Randwick, Sydney, NSW, Australia.,University of New South Wales Clinical School, Sydney, NSW, Australia
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21
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Dolgun ZN, Kabaca C, Karateke A, İyibozkurt C, İnan C, Altıntaş AS, Karadağ C. The Use of Human Epididymis 4 and Cancer Antigen 125 Tumor Markers in the Benign or Malignant Differential Diagnosis of Pelvic or Adnexal Masses. Balkan Med J 2018; 34:156-162. [PMID: 28418343 PMCID: PMC5394297 DOI: 10.4274/balkanmedj.2016.0223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Ovarian cancer is one of the highest mortality cancers in gynaecology. Discrimination of benign masses from malignant ones may sometimes become a challenge for the clinician since there is not a reliable tumour marker, thus some unnecessary, highly morbid operations can be performed. AIMS To explore the efficacy of human epididymis 4 (HE 4) and cancer antigen 125 (CA 125) markers in differentiating malignant and benign pelvic masses of ovarian origin and to identify the cut-off points for those markers. STUDY DESIGN Prospective study. METHODS Fifty-one patients who were diagnosed and planned to undergo surgery for ovarian mass between June 2008 and December 2008 were enrolled into this study. Preoperative venous blood samples were taken and frozen for marker investigation and final diagnoses were concluded by histopathological examination. After recruitment of all cases CA 125 and HE 4 levels were evaluated. RESULTS The statistical analysis did not indicate any statistically significant difference between the CA 125 levels of the patients with malignant and benign adnexal masses (p=0.105). The HE 4 levels of the patients with malignant adnexal masses were higher at a statistically significant level compared to the patients with benign adnexal masses (p=0.002). For HE 4 tumour marker and at the cut-off point of >25 pM, sensitivity was 1, specificity 0.40, positive cut-off value 0.19, negative cut-off value 1, accuracy 0.47 and positive likelihood ratio 1.65. CONCLUSION Human epididymis 4 is a better diagnostic tool than CA 125 in benign-malignant discrimination of adnexal masses. The cut-off value of 25 pmol/L for human epididymis 4 will contribute to providing proper guidance to patients with adnexal masses and applying the proper treatment method.
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Affiliation(s)
- Zehra Nihal Dolgun
- Clinic of Obstetrics and Gynecology, Zeynep Kamil Women and Children's Training and Research Hospital, İstanbul, Turkey
| | - Canan Kabaca
- Clinic of Obstetrics and Gynecology, Zeynep Kamil Women and Children's Training and Research Hospital, İstanbul, Turkey
| | - Ateş Karateke
- Clinic of Obstetrics and Gynecology, Zeynep Kamil Women and Children's Training and Research Hospital, İstanbul, Turkey
| | - Cem İyibozkurt
- Department of Obstetrics and Gynecology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Cihan İnan
- Department of Obstetrics and Gynecology, Trakya University School of Medicine, Edirne, Turkey
| | - Ahmet Salih Altıntaş
- Department of Obstetrics and Gynecology, Trakya University School of Medicine, Edirne, Turkey
| | - Cihan Karadağ
- Department of Obstetrics and Gynecology, Marmara University Training and Research Hospital, İstanbul, Turkey
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22
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Jacobs I. Steady, relentless progress towards effective, safe screening for early detection of cancer of the ovary. BJOG 2018; 125:526-528. [DOI: 10.1111/1471-0528.14830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2017] [Indexed: 11/28/2022]
Affiliation(s)
- I Jacobs
- University of New South Wales; Sydney NSW Australia
- Department of Women's Cancer; Institute for Women's Health; University College London; London UK
- Centre for Women's Health; Institute of Human Development; University of Manchester; Manchester UK
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23
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Campbell S, Gentry-Maharaj A. The role of transvaginal ultrasound in screening for ovarian cancer. Climacteric 2018; 21:221-226. [PMID: 29490504 DOI: 10.1080/13697137.2018.1433656] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Ovarian cancer is a low-prevalence postmenopausal cancer with a high mortality rate and is the fifth most lethal cancer in women. The most common serous subtype with TP53 mutations spreads rapidly throughout the peritoneal cavity (stage III/IV) when 5-year survival is 10%. If diagnosed while confined to the ovary (stage I), the survival rate exceeds 90%. This is the rationale for screening. Annual transvaginal ultrasound (TVU) scans used as a primary screening modality or as a second-line test following primary screening with serum CA125 (multimodal) have been investigated in several trials. Only two large randomized controlled trials have provided mortality data. The US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial studied over 78 000 women (randomized to screening with either TVU or CA125, or control) over 6 years with 14 years follow-up and found no mortality benefit from screening and increased morbidity in the screened arm. The UK Collaborative Trial of Ovarian Cancer Screening studied over 202 000 women randomized to TVU, multimodal or control in a 1 : 1 : 2 ratio over 7-11 years with 11 years follow-up. CA125 was interpreted by the Risk of Ovarian Cancer algorithm which identifies a rise in the level rather than a fixed cut-off. There was a late reduction in mortality after 7 years in the screened arm (23% in the multimodal arm and 21% in the TVU arm), but the overall reduction was not significant. Further follow-up may reveal whether TVU has a primary or secondary role in ovarian cancer screening.
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Affiliation(s)
| | - A Gentry-Maharaj
- b Gynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health , University College London , London , UK
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24
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Abramowicz JS, Timmerman D. Ovarian mass-differentiating benign from malignant: the value of the International Ovarian Tumor Analysis ultrasound rules. Am J Obstet Gynecol 2017; 217:652-660. [PMID: 28735703 DOI: 10.1016/j.ajog.2017.07.019] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Revised: 07/10/2017] [Accepted: 07/15/2017] [Indexed: 12/16/2022]
Abstract
Ovarian cancer, the fifth most common cause of cancer death among women, has the highest mortality rate of all gynecologic cancers. General survival rate is <50% but can reach 90% if disease is detected early. Ultrasound is presently the best modality to differentiate between benign and malignant status. The patient with a malignant mass should be referred to an oncology surgeon since results have been shown to be superior to treatment by a specialist. Several ultrasound-based scoring systems exist for assessing the risk of an ovarian tumor to be malignant. The International Ovarian Tumor Analysis group published 2 such systems: the ultrasound Simple Rules and the Assessment of Different NEoplasias in the adneXa model. The Simple Rules classifies a tumor as benign, malignant, or indeterminate and the Assessment of Different NEoplasias in the adneXa model determines the risk for a tumor to be benign or malignant and, if malignant, the risk of various stages. Sensitivity of the Simple Rules and Assessment of Different NEoplasias in the adneXa model (using a cut-off of 10% to predict malignancy) are 92% and 96.5%, respectively, and specificities are 96% and 71.3%, respectively. These models are the best predictive tests for the preoperative classification of adnexal tumors. Their intent is to help the specialist make management decisions when faced with a patient with a persistent ovarian mass. The models are simple, are easy to use, and have been validated in multiple reports but not in the United States. We suggest they should be validated and widely introduced into medical practice in the United States.
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25
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Pandharipande PV, Lowry KP, Reinhold C, Atri M, Benson CB, Bhosale PR, Green ED, Kang SK, Lakhman Y, Maturen KE, Nicola R, Salazar GM, Shipp TD, Simpson L, Sussman BL, Uyeda J, Wall DJ, Whitcomb B, Zelop CM, Glanc P. ACR Appropriateness Criteria ® Ovarian Cancer Screening. J Am Coll Radiol 2017; 14:S490-S499. [DOI: 10.1016/j.jacr.2017.08.049] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 08/23/2017] [Indexed: 11/27/2022]
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26
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Ring KL, Garcia C, Thomas MH, Modesitt SC. Current and future role of genetic screening in gynecologic malignancies. Am J Obstet Gynecol 2017; 217:512-521. [PMID: 28411145 DOI: 10.1016/j.ajog.2017.04.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 03/28/2017] [Accepted: 04/04/2017] [Indexed: 02/06/2023]
Abstract
The world of hereditary cancers has seen exponential growth in recent years. While hereditary breast and ovarian cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate risk-reduction strategies. Given the speed of information, it is imperative to involve cancer genetics experts when counseling these patients. In addition, coordination of screening and care in conjunction with specialty high-risk clinics, if available, allows for patients to have centralized management for multiple cancer risks under the guidance of physicians with experience counseling these patients. The objective of this review is to present the current literature regarding genetic mutations associated with gynecologic malignancies as well to propose screening and risk-reduction options for these high-risk patients.
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27
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28
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Yokoi A, Yoshioka Y, Hirakawa A, Yamamoto Y, Ishikawa M, Ikeda SI, Kato T, Niimi K, Kajiyama H, Kikkawa F, Ochiya T. A combination of circulating miRNAs for the early detection of ovarian cancer. Oncotarget 2017; 8:89811-89823. [PMID: 29163790 PMCID: PMC5685711 DOI: 10.18632/oncotarget.20688] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 07/25/2017] [Indexed: 02/06/2023] Open
Abstract
Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine.
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Affiliation(s)
- Akira Yokoi
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yusuke Yoshioka
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Akihiro Hirakawa
- Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yusuke Yamamoto
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Mitsuya Ishikawa
- Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shun-ichi Ikeda
- Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoyasu Kato
- Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan
| | - Kaoru Niimi
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroaki Kajiyama
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Fumitaka Kikkawa
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
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29
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Committee Opinion No. 716: The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer in Women at Average Risk. Obstet Gynecol 2017; 130:e146-e149. [PMID: 28832487 DOI: 10.1097/aog.0000000000002299] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian cancer syndrome (BRCA mutation) or hereditary nonpolyposis colorectal cancer (Lynch syndrome), and these women are at increased risk of developing ovarian cancer. Women with these conditions should be referred for formal genetic counseling to better assess their cancer risk, including their risk of ovarian cancer. If appropriate, these women may be offered additional testing for early detection of ovarian cancer. The use of transvaginal ultrasonography and tumor markers (such as cancer antigen 125), alone or in combination, for the early detection of ovarian cancer in average-risk women have not been proved to reduce mortality, and harms exist from invasive diagnostic testing (eg, surgery) resulting from false-positive test results. The patient and her obstetrician-gynecologist should maintain an appropriate level of suspicion when potentially relevant signs and symptoms of ovarian cancer are present.
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30
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Kristeleit R, Davidenko I, Shirinkin V, El-Khouly F, Bondarenko I, Goodheart MJ, Gorbunova V, Penning CA, Shi JG, Liu X, Newton RC, Zhao Y, Maleski J, Leopold L, Schilder RJ. A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)–only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer. Gynecol Oncol 2017; 146:484-490. [DOI: 10.1016/j.ygyno.2017.07.005] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2017] [Revised: 06/30/2017] [Accepted: 07/04/2017] [Indexed: 12/31/2022]
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Englert-Golon M, Burchardt B, Budny B, Dębicki S, Majchrzycka B, Wrotkowska E, Jasiński P, Ziemnicka K, Słopień R, Ruchała M, Sajdak S. Genomic markers of ovarian adenocarcinoma and its relevancy to the effectiveness of chemotherapy. Oncol Lett 2017; 14:3401-3414. [PMID: 28927094 PMCID: PMC5588060 DOI: 10.3892/ol.2017.6590] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 04/13/2017] [Indexed: 02/06/2023] Open
Abstract
Ovarian cancer is the eighth most common cancer and the seventh highest cause of cancer-associated mortality in women worldwide. It is the second highest cause of mortality among female reproductive malignancies. The current standard first-line treatment for advanced ovarian cancer includes a combination of surgical debulking and standard systemic platinum-based chemotherapy with carboplatin and paclitaxel. Although a deeper understanding of this disease has been attained, relapse occurs in 70% of patients 18 months subsequent to the first-line treatment. Therefore, it is crucial to develop a novel drug that effectively affects ovarian cancer, particularly tumors that are resistant to current chemotherapy. The aim of the present study was to identify genes whose expression may be used to predict survival time or prognosis in ovarian cancer patients treated with chemotherapy. Gene or protein expression is an important issue in chemoresistance and survival prediction in ovarian cancer. In the present study, the research group consisted of patients treated at the Surgical Clinic of the Gynecology and Obstetrics Gynecological Clinical Hospital, Poznan University of Medical Sciences (Poznan, Poland) between May 2006 and November 2014. Additional eligibility criteria were a similar severity (International Federation of Gynecolgy and Obstetrics stage III) at the time of diagnosis, treatment undertaken in accordance with the same schedule, and an extremely good response to treatment or a lack of response to treatment. The performance of the OncoScan® assay was evaluated by running the assay on samples obtained from the four patients and by following the recommended protocol outlined in the OncoScan assay manual. The genomic screening using Affymetrix OncoScan Arrays resulted in the identification of large genomic rearrangements across all cancer tissues. In general, chromosome number changes were detected in all examined tissues. The OncoScan arrays enabled the identification of ~100 common somatic mutations. Chemotherapy response in ovarian cancer is extremely complex and challenging to study. The present study identified specific genetic alterations associated with ovarian cancer, but not with response for treatment.
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Affiliation(s)
- Monika Englert-Golon
- Surgical Gynecology Clinic of The Gynecological and Obstetrics Clinical Hospital, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Bartosz Burchardt
- Surgical Gynecology Clinic of The Gynecological and Obstetrics Clinical Hospital, Poznan University of Medical Sciences, 60-535 Poznan, Poland.,Department of Forensic Sciences, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Bartlomiej Budny
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Szymon Dębicki
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Blanka Majchrzycka
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Elzbieta Wrotkowska
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Piotr Jasiński
- Gynecological and Obstetrics Clinical Hospital, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Katarzyna Ziemnicka
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Radosław Słopień
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Marek Ruchała
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Stefan Sajdak
- Surgical Gynecology Clinic of The Gynecological and Obstetrics Clinical Hospital, Poznan University of Medical Sciences, 60-535 Poznan, Poland
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32
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Montagnana M, Benati M, Danese E. Circulating biomarkers in epithelial ovarian cancer diagnosis: from present to future perspective. ANNALS OF TRANSLATIONAL MEDICINE 2017; 5:276. [PMID: 28758102 DOI: 10.21037/atm.2017.05.13] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Ovarian cancer (OC) represents the most lethal gynecological cancer and the poor prognosis is often attributable to late diagnosis. The diagnostic approach to woman presenting with pelvic mass is difficult and differential diagnosis often requires invasive histological examination. Serum CA125 and HE4, as well as the most of the other serum biomarkers discovered and validated, are not sufficiently sensitive and specific to make early diagnosis. Moreover, conflicting results exist about the improvement of diagnostic performance by using multivariate index assays, developed by combining circulating biomarkers with other variables (i.e., ultrasound and/or menopausal status and/or age), in comparison to CA125 or HE4 alone. In the last years, several studies focused on the microRNAs (miRs), short single-stranded non-coding RNA that regulate several messenger RNAs (mRNAs). As in other cancer types, the aberrant miRs expression has been demonstrated in gynecological cancers, in both tissues and serum samples. In particular, the diagnostic performance of single or miRs panels resulted very high. However, to date, despite the potential clinical utility has been demonstrated, none of these miRs has been validated in large OC populations.
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Affiliation(s)
- Martina Montagnana
- Clinical Biochemistry Section, University Hospital of Verona, Verona, Italy
| | - Marco Benati
- Clinical Biochemistry Section, University Hospital of Verona, Verona, Italy
| | - Elisa Danese
- Clinical Biochemistry Section, University Hospital of Verona, Verona, Italy
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33
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Yang WL, Lu Z, Bast RC. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn 2017; 17:577-591. [PMID: 28468520 DOI: 10.1080/14737159.2017.1326820] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Despite advances in surgery and chemotherapy for ovarian cancer, 70% of women still succumb to the disease. Biomarkers have contributed to the management of ovarian cancer by monitoring response to treatment, detecting recurrence, distinguishing benign from malignant pelvic masses and attempting to detect disease at an earlier stage. Areas covered: This review focuses on recent advances in biomarkers and imaging for management of ovarian cancer with particular emphasis on early detection. Relevant literature has been reviewed and analyzed. Expert commentary: Rising or persistent CA125 blood levels provide a highly specific biomarker for epithelial ovarian cancer, but not an optimally sensitive biomarker. Addition of HE4, CA 72.4, anti-TP53 autoantibodies and other biomarkers can increase sensitivity for detecting early stage or recurrent disease. Detecting disease recurrence will become more important as more effective therapy is developed. Early detection will require the development not only of biomarker panels, but also of more sensitive and specific imaging strategies. Effective biomarker strategies are already available for distinguishing benign from malignant pelvic masses, but their use in identifying and referring patients with probable ovarian cancer to gynecologic oncologists for cytoreductive operations must be encouraged.
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Affiliation(s)
- Wei-Lei Yang
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.,b Odyssey Program , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Zhen Lu
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Robert C Bast
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
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Yang WL, Lu Z, Bast RC. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn 2017. [PMID: 28468520 DOI: 10.1080/14737159.2017.1326820] [] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Despite advances in surgery and chemotherapy for ovarian cancer, 70% of women still succumb to the disease. Biomarkers have contributed to the management of ovarian cancer by monitoring response to treatment, detecting recurrence, distinguishing benign from malignant pelvic masses and attempting to detect disease at an earlier stage. Areas covered: This review focuses on recent advances in biomarkers and imaging for management of ovarian cancer with particular emphasis on early detection. Relevant literature has been reviewed and analyzed. Expert commentary: Rising or persistent CA125 blood levels provide a highly specific biomarker for epithelial ovarian cancer, but not an optimally sensitive biomarker. Addition of HE4, CA 72.4, anti-TP53 autoantibodies and other biomarkers can increase sensitivity for detecting early stage or recurrent disease. Detecting disease recurrence will become more important as more effective therapy is developed. Early detection will require the development not only of biomarker panels, but also of more sensitive and specific imaging strategies. Effective biomarker strategies are already available for distinguishing benign from malignant pelvic masses, but their use in identifying and referring patients with probable ovarian cancer to gynecologic oncologists for cytoreductive operations must be encouraged.
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Affiliation(s)
- Wei-Lei Yang
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.,b Odyssey Program , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Zhen Lu
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Robert C Bast
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
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Yang WL, Lu Z, Bast RC. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn 2017. [PMID: 28468520 DOI: 10.1080/14737159.2017.1326820]+[] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2022]
Abstract
INTRODUCTION Despite advances in surgery and chemotherapy for ovarian cancer, 70% of women still succumb to the disease. Biomarkers have contributed to the management of ovarian cancer by monitoring response to treatment, detecting recurrence, distinguishing benign from malignant pelvic masses and attempting to detect disease at an earlier stage. Areas covered: This review focuses on recent advances in biomarkers and imaging for management of ovarian cancer with particular emphasis on early detection. Relevant literature has been reviewed and analyzed. Expert commentary: Rising or persistent CA125 blood levels provide a highly specific biomarker for epithelial ovarian cancer, but not an optimally sensitive biomarker. Addition of HE4, CA 72.4, anti-TP53 autoantibodies and other biomarkers can increase sensitivity for detecting early stage or recurrent disease. Detecting disease recurrence will become more important as more effective therapy is developed. Early detection will require the development not only of biomarker panels, but also of more sensitive and specific imaging strategies. Effective biomarker strategies are already available for distinguishing benign from malignant pelvic masses, but their use in identifying and referring patients with probable ovarian cancer to gynecologic oncologists for cytoreductive operations must be encouraged.
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Affiliation(s)
- Wei-Lei Yang
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.,b Odyssey Program , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Zhen Lu
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Robert C Bast
- a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
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Fallowfield L, Solis-Trapala I, Menon U, Langridge C, May S, Jacobs I, Jenkins V. The effect of ovarian cancer screening on sexual activity and functioning: results from the UK collaborative trial of ovarian cancer screening RCT. Br J Cancer 2017; 116:1111-1117. [PMID: 28324886 PMCID: PMC5396121 DOI: 10.1038/bjc.2017.72] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 02/01/2017] [Accepted: 02/22/2017] [Indexed: 01/27/2023] Open
Abstract
Background: To examine the impact of multimodal (MMS) and ultrasound (USS) screening on the sexual activity and functioning of 22 966 women in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) RCT. Methods: Fallowfield's Sexual Activity Questionnaire (FSAQ) was completed prior to randomisation, then annually in a random sample (RS) of women from MMS, USS and control groups. Any women in the study who required repeat screening due to unsatisfactory results formed an Events Sample (ES); they completed questionnaires following an event and annually thereafter. Results: Over time in the RS (n=1339) there was no difference between the MMS and USS groups in sexual activity compared with controls. In the ES there were significant differences between the USS group (n=10 156) and the MMS group (n=12 810). The USS group had lower pleasure scores (mean difference=−0.14, P=0.046). For both groups women who had ⩾2 repeat screens, showed a decrease in mean pleasure scores compared with their annual scores (mean difference=−0.16, P=0.005). Similarly mean pleasure scores decreased following more intensive screens compared with annual screening (mean difference=−0.09, P=0.046). Conclusions: Ovarian cancer screening did not affect sexual activity and functioning unless a woman had abnormal results and underwent repeated or higher level screening.
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Affiliation(s)
- Lesley Fallowfield
- Sussex Health Outcomes Research & Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9RX, UK
| | - Ivonne Solis-Trapala
- Institute for Applied Clinical Sciences, Guy Hilton Research Centre, Keele University, Newcastle ST4 7QB, UK
| | - Usha Menon
- Department of Women's Cancer, Institute for Women's Health, University College London, London W1T 7DN, UK
| | - Carolyn Langridge
- Sussex Health Outcomes Research & Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9RX, UK
| | - Shirley May
- Sussex Health Outcomes Research & Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9RX, UK
| | - Ian Jacobs
- Department of Women's Cancer, Institute for Women's Health, University College London, London W1T 7DN, UK.,University of New South Wales, Sydney, NSW 2052, Australia
| | - Valerie Jenkins
- Sussex Health Outcomes Research & Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9RX, UK
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Skates SJ, Greene MH, Buys SS, Mai PL, Brown P, Piedmonte M, Rodriguez G, Schorge JO, Sherman M, Daly MB, Rutherford T, Brewster WR, O'Malley DM, Partridge E, Boggess J, Drescher CW, Isaacs C, Berchuck A, Domchek S, Davidson SA, Edwards R, Elg SA, Wakeley K, Phillips KA, Armstrong D, Horowitz I, Fabian CJ, Walker J, Sluss PM, Welch W, Minasian L, Horick NK, Kasten CH, Nayfield S, Alberts D, Finkelstein DM, Lu KH. Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials. Clin Cancer Res 2017; 23:3628-3637. [PMID: 28143870 DOI: 10.1158/1078-0432.ccr-15-2750] [Citation(s) in RCA: 94] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 01/18/2017] [Accepted: 01/25/2017] [Indexed: 01/15/2023]
Abstract
Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL.Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years).Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR.
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Affiliation(s)
| | | | - Saundra S Buys
- Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah
| | | | | | | | | | | | | | - Mary B Daly
- Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | | | | | - David M O'Malley
- Ohio State University and the James Cancer Center, Columbus, Ohio
| | - Edward Partridge
- University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama
| | | | | | - Claudine Isaacs
- Georgetown University Medical Center, Lombardi Cancer Center, Washington, District of Columbia
| | - Andrew Berchuck
- Duke University Medical Center, Division of Gynecologic Oncology, Durham, North Carolina
| | - Susan Domchek
- University of Pennsylvania, Abramson Cancer Center, Philadelphia, Pennsylvania
| | | | | | - Steven A Elg
- The Iowa Clinic, Gynecologic Oncology, Des Moines, Iowa
| | - Katie Wakeley
- Dana-Farber Cancer Center in Clinical Affiliation with South Shore Hospital, South Weymouth, Massachusetts
| | - Kelly-Anne Phillips
- Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia.,Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.,Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
| | | | - Ira Horowitz
- Emory University School of Medicine, Atlanta, Georgia
| | - Carol J Fabian
- The University of Kansas Cancer Center, Westwood, Kansas
| | - Joan Walker
- Stephenson Cancer Center, University of Oklahoma HSC, Oklahoma City, Oklahoma
| | | | | | | | - Nora K Horick
- Massachusetts General Hospital, Boston, Massachusetts
| | | | | | - David Alberts
- University of Arizona Cancer Center, Tucson, Arizona
| | | | - Karen H Lu
- MD Anderson Cancer Center, Houston, Texas
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Mueller JJ, Kelly A, Zhou Q, Iasonos A, Long Roche K, Sonoda Y, O'Cearbhaill RE, Zivanovic O, Chi DS, Gardner GJ. Intraperitoneal chemotherapy after interval debulking surgery for advanced-stage ovarian cancer: Feasibility and outcomes at a comprehensive cancer center. Gynecol Oncol 2016; 143:496-503. [PMID: 27692668 DOI: 10.1016/j.ygyno.2016.09.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 09/09/2016] [Accepted: 09/12/2016] [Indexed: 10/20/2022]
Abstract
OBJECTIVES Intraperitoneal (IP)-based chemotherapy following primary debulking surgery (PDS), although associated with substantial toxicity, is supported by a strong evidence base. We sought to determine feasibility and outcomes of IP chemotherapy after interval debulking surgery (IDS) among patients deemed ineligible for PDS. METHODS We identified all patients with high-grade, stage III/IV ovarian cancer treated at our institution with neoadjuvant chemotherapy (NACT) followed by IDS and postoperative chemotherapy from 1/2008-5/2013. IP and intravenous (IV) regimens were defined; demographic and clinical data were analyzed using appropriate statistics. RESULTS Of 128 evaluable patients, 118 (92%) achieved ≤1cm residual disease at IDS and 74 (58%) achieved a complete gross resection (CGR). An IP port was placed in 54/128 patients (42%), with 89% port utilization. Forty-eight (38%) of 128 patients received IP chemotherapy, 17 (13%) weekly IV paclitaxel/q3week carboplatin, and 63 (49%) q3week IV carboplatin/paclitaxel. Patients completed a median of 3 IP cycles (range, 2-6), with 3 (5.5%) of 54 ports removed due to complications. Overall survival (OS) for patients with a CGR treated with IP and weekly IV chemotherapy was 53.2months (range, 24.7-NE), and 44.2months (range, 30.2-NE) with any visible residual disease (p<0.001). Median OS was 53.2months (range, 44.5-NE) for IP-, not reached for weekly IV-, and 34.2months (range, 27.5-49.8) for q3week IV-treated patients (p=0.1). CONCLUSIONS Patients administered IP after IDS had a high rate of successful port utilization, with few regimen switches. Oncologic outcomes were optimal in patients with a CGR at IDS, regardless of chemotherapy used.
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Affiliation(s)
- Jennifer J Mueller
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Amelia Kelly
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Qin Zhou
- Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alexia Iasonos
- Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kara Long Roche
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Yukio Sonoda
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Roisin E O'Cearbhaill
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Oliver Zivanovic
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Dennis S Chi
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Ginger J Gardner
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
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Skates SJ. EPIC Early Detection of Ovarian Cancer. Clin Cancer Res 2016; 22:4542-4. [PMID: 27418634 DOI: 10.1158/1078-0432.ccr-16-1391] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 07/07/2016] [Indexed: 11/16/2022]
Abstract
CA125 dominated performance for ovarian cancer early detection among four serum biomarkers evaluated in EPIC study prediagnostic serum, rising on average 3 years prior to detection. Adding HE4 provided only marginal improvement. This natural history supports annual testing for early detection and highlights the importance of biomarker discovery complementing CA125. Clin Cancer Res; 22(18); 4542-4. ©2016 AACRSee related article by Terry et al., p. 4664.
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Affiliation(s)
- Steven J Skates
- Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
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Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, Amso NN, Apostolidou S, Benjamin E, Cruickshank D, Crump DN, Davies SK, Dawnay A, Dobbs S, Fletcher G, Ford J, Godfrey K, Gunu R, Habib M, Hallett R, Herod J, Jenkins H, Karpinskyj C, Leeson S, Lewis SJ, Liston WR, Lopes A, Mould T, Murdoch J, Oram D, Rabideau DJ, Reynolds K, Scott I, Seif MW, Sharma A, Singh N, Taylor J, Warburton F, Widschwendter M, Williamson K, Woolas R, Fallowfield L, McGuire AJ, Campbell S, Parmar M, Skates SJ. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet 2016; 387:945-956. [PMID: 26707054 PMCID: PMC4779792 DOI: 10.1016/s0140-6736(15)01224-6] [Citation(s) in RCA: 709] [Impact Index Per Article: 78.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. METHODS In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. FINDINGS Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS. INTERPRETATION Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. FUNDING Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.
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Affiliation(s)
- Ian J Jacobs
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; University of New South Wales, Sydney, NSW, Australia; Centre for Women's Health, Institute of Human Development, University of Manchester, Manchester, UK.
| | - Usha Menon
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK.
| | - Andy Ryan
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | | | - Matthew Burnell
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Jatinderpal K Kalsi
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Nazar N Amso
- Obstetrics and Gynaecology, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
| | - Sophia Apostolidou
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Elizabeth Benjamin
- Research Department of Pathology, Cancer Institute, University College London Hospital, London, UK
| | - Derek Cruickshank
- Department of Gynaecological Oncology, James Cook University Hospital, Middlesbrough, UK
| | - Danielle N Crump
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Susan K Davies
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Anne Dawnay
- Clinical Biochemistry, University College London Hospital, London, UK
| | - Stephen Dobbs
- Department of Gynaecological Oncology, Belfast City Hospital, Belfast, UK
| | - Gwendolen Fletcher
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Jeremy Ford
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Malomatia (Information, Communication and Technology QATAR) Qatari Shareholding Company, Qatar
| | - Keith Godfrey
- Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK
| | - Richard Gunu
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Mariam Habib
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Medical Research Council Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK
| | - Rachel Hallett
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; School of Medical Sciences, Bangor University, Bangor, Gwynedd, UK
| | - Jonathan Herod
- Department of Gynaecology, Liverpool Women's Hospital, Liverpool, UK; Women's Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Howard Jenkins
- Department of Gynaecological Oncology, Royal Derby Hospital, Derby, UK
| | - Chloe Karpinskyj
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Simon Leeson
- Department of Gynaecological Oncology, Llandudno Hospital, Gwynedd, UK
| | - Sara J Lewis
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - William R Liston
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Alberto Lopes
- Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK; Derriford Hospital, Plymouth, Devon, UK
| | - Tim Mould
- Department of Gynaecological Oncology, University College London Hospital, London, UK; Department of Gynaecological Oncology, Royal Free Hospital, London
| | - John Murdoch
- Department of Gynaecological Oncology, St Michael's Hospital, Bristol, UK
| | - David Oram
- Department of Gynaecological Oncology, St Bartholomew's Hospital, London, UK
| | - Dustin J Rabideau
- Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA
| | - Karina Reynolds
- Department of Gynaecological Oncology, St Bartholomew's Hospital, London, UK
| | - Ian Scott
- Department of Gynaecological Oncology, Royal Derby Hospital, Derby, UK
| | - Mourad W Seif
- Central Manchester Foundation Trust, St Mary's Hospital, Manchester, UK; Institute of Cancer Sciences, University of Manchester, Manchester, UK
| | - Aarti Sharma
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Department of Gynaecological Oncology, University Hospital of Wales, Heath Park, Cardiff, UK
| | - Naveena Singh
- Department of Pathology, Barts Health National Health Service Trust, London, UK
| | - Julie Taylor
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Fiona Warburton
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Public Health England, London, UK
| | - Martin Widschwendter
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
| | - Karin Williamson
- Department of Gynaecological Oncology, Nottingham City Hospital, Nottingham, UK
| | - Robert Woolas
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Department of Gynaecological Oncology, Queen Alexandra Hospital, Portsmouth, Hampshire, UK
| | - Lesley Fallowfield
- Sussex Health Outcomes Research and Education in Cancer, Brighton and Sussex Medical School, University of Sussex, Sussex, UK
| | | | | | - Mahesh Parmar
- Medical Research Council Clinical Trials Unit at University College London, London, UK
| | - Steven J Skates
- Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
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Affiliation(s)
- Mike Fisher
- Abcodia Ltd, 1010 Cambourne Business Park, Cambourne, Cambridge CB23 6DP, UK
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43
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Menon U, Ryan A, Kalsi J, Gentry-Maharaj A, Dawnay A, Habib M, Apostolidou S, Singh N, Benjamin E, Burnell M, Davies S, Sharma A, Gunu R, Godfrey K, Lopes A, Oram D, Herod J, Williamson K, Seif MW, Jenkins H, Mould T, Woolas R, Murdoch JB, Dobbs S, Amso NN, Leeson S, Cruickshank D, Scott I, Fallowfield L, Widschwendter M, Reynolds K, McGuire A, Campbell S, Parmar M, Skates SJ, Jacobs I. Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. J Clin Oncol 2015; 33:2062-71. [PMID: 25964255 PMCID: PMC4463475 DOI: 10.1200/jco.2014.59.4945] [Citation(s) in RCA: 152] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. PATIENTS AND METHODS In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. RESULTS After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). CONCLUSION Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.
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Affiliation(s)
- Usha Menon
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia.
| | - Andy Ryan
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Jatinderpal Kalsi
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Aleksandra Gentry-Maharaj
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Anne Dawnay
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Mariam Habib
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Sophia Apostolidou
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Naveena Singh
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Elizabeth Benjamin
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Matthew Burnell
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Susan Davies
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Aarti Sharma
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Richard Gunu
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Keith Godfrey
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Alberto Lopes
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - David Oram
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Jonathan Herod
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Karin Williamson
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Mourad W Seif
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Howard Jenkins
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Tim Mould
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Robert Woolas
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - John B Murdoch
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Stephen Dobbs
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Nazar N Amso
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Simon Leeson
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Derek Cruickshank
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Ian Scott
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Lesley Fallowfield
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Martin Widschwendter
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Karina Reynolds
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Alistair McGuire
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Stuart Campbell
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Mahesh Parmar
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Steven J Skates
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
| | - Ian Jacobs
- Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia
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Hasanbegovic L, Alicelebic S, Sljivo N. Comparison of specific ovarian tumor markers by elecsys analyzer 2010. Acta Inform Med 2015; 23:86-9. [PMID: 26005273 PMCID: PMC4430012 DOI: 10.5455/aim.2015.23.86-89] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 04/05/2015] [Indexed: 11/03/2022] Open
Abstract
Background: the most widely used tumor marker in ovarian cancer, often considered the ‘gold standard’ is CA125 but reliable clinical evidence demonstrates that human epididymis protein (HE4), used alone or in combination with CA125, substantially improves the accuracy of screening and/or disease monitoring. Aim: to evaluate the reliability of the determination a tumor marker HE4 in comparison with CA125 on the Elecsys analyzer 2010 in epithelial ovarian cancer, benign ovarian cyst and healthy controls. Methods: we prospectively determined CA125 and HE4 serum levels in the Biochemical-Immunological-Haematological “Medical Laboratory” Ilidza, Sarajevo, B&H between June 1st and December 31st 2011. Electro-chemiluminescence immunoassay (ECLIA) methods for quantitative determination in vitro were performed on the Roche/Hitachi Elecsys 2010 Immunoassay Analyzer. Standard methods of descriptive statistics were performed for the data analysis. Results: univariate statistical analyze of tumor marker control serum revealed a high reliability for both CA125 and HE4 determination (p>0.05). Levey-Jennings charts of quality control data show that the target and the obtained values of both markers control sera do not differ significantly in relation to the ideal value. In a total number of 60 patients compared values of tumor markers show a high correlation (r=0.85). This study confirmed higher sensitivity and specificity of HE4 tumor marker compared with CA125. ROC-AUC values show that the diagnostic performance of HE4 was significantly higher compared with CA125. Conclusion: We concluded that HE4 was better than CA125 as a single tumor marker.
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Affiliation(s)
- Lejla Hasanbegovic
- Biochemical-Immunological-Haematological "Medical Laboratory" Ilidza, Sarajevo, Bosnia and Herzegovina
| | - Selma Alicelebic
- Institute of Histology and Embryology, School of Medicine, Sarajevo, Bosnia and Herzegovina
| | - Nedeljka Sljivo
- Institute of Histology and Embryology, School of Medicine, Sarajevo, Bosnia and Herzegovina
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Abstract
Screening for premalignant lesions or early invasive disease has the potential to reduce mortality from cancer. Because of their ease of measurement, several biomarkers have been evaluated or are currently undergoing evaluation as screening tests for early malignancy. These include the use of AFP in screening for hepatocellular cancer in high-risk subjects, CA 125 in combination with transvaginal ultrasound (TVU) in screening for epithelial ovarian cancer, PSA in screening for prostate cancer, faecal occult blood testing (FOBT) in screening for colorectal cancer (CRC) and vanillymandelic acid and homovanillic acid in screening for neuroblastoma in newborn infants, Of these biomarkers, only the use of FOBT in screening for CRC has unequivocally been shown to reduce mortality from cancer. Although 2 large randomized prospective trials have evaluated PSA as a screening test for prostate cancer, it is still unclear whether the benefits outweigh the harms in this setting. Although biomarkers have many attractive features as cancer screening tests, lack of sensitivity and specificity, when combined with the low prevalence of specific cancer types in asymptomatic subjects, limit their application for the early detection of malignancy.
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Affiliation(s)
- Michael J Duffy
- Clinical Research Centre, St Vincent's University Hospital, Elm Park, Dublin, 4, Ireland.
- UCD School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, 4, Ireland.
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Wan YL, Crosbie EJ. Commentary on ‘Performance of ultrasound as a second line test to serum CA125 in ovarian cancer screening’. BJOG 2014; 121 Suppl 7:40-7. [DOI: 10.1111/1471-0528.13154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/11/2014] [Indexed: 11/30/2022]
Affiliation(s)
- YL Wan
- Institute of Cancer Sciences; University of Manchester; St Mary's Hospital; Manchester UK
| | - EJ Crosbie
- Institute of Cancer Sciences; University of Manchester; St Mary's Hospital; Manchester UK
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Shadfan BH, Simmons AR, Simmons GW, Ho A, Wong J, Lu KH, Bast RC, McDevitt JT. A multiplexable, microfluidic platform for the rapid quantitation of a biomarker panel for early ovarian cancer detection at the point-of-care. Cancer Prev Res (Phila) 2014; 8:37-48. [PMID: 25388014 DOI: 10.1158/1940-6207.capr-14-0248] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Point-of-care (POC) diagnostic platforms have the potential to enable low-cost, large-scale screening. As no single biomarker is shed by all ovarian cancers, multiplexed biomarker panels promise improved sensitivity and specificity to address the unmet need for early detection of ovarian cancer. We have configured the programmable bio-nano-chip (p-BNC)-a multiplexable, microfluidic, modular platform-to quantify a novel multi-marker panel comprising CA125, HE4, MMP-7, and CA72-4. The p-BNC is a bead-based immunoanalyzer system with a credit-card-sized footprint that integrates automated sample metering, bubble and debris removal, reagent storage and waste disposal, permitting POC analysis. Multiplexed p-BNC immunoassays demonstrated high specificity, low cross-reactivity, low limits of detection suitable for early detection, and a short analysis time of 43 minutes. Day-to-day variability, a critical factor for longitudinally monitoring biomarkers, ranged between 5.4% and 10.5%, well below the biologic variation for all four markers. Biomarker concentrations for 31 late-stage sera correlated well (R(2) = 0.71 to 0.93 for various biomarkers) with values obtained on the Luminex platform. In a 31 patient cohort encompassing early- and late-stage ovarian cancers along with benign and healthy controls, the multiplexed p-BNC panel was able to distinguish cases from controls with 68.7% sensitivity at 80% specificity. Utility for longitudinal biomarker monitoring was demonstrated with prediagnostic plasma from 2 cases and 4 controls. Taken together, the p-BNC shows strong promise as a diagnostic tool for large-scale screening that takes advantage of faster results and lower costs while leveraging possible improvement in sensitivity and specificity from biomarker panels.
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Affiliation(s)
| | - Archana R Simmons
- Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas
| | - Glennon W Simmons
- Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas
| | - Andy Ho
- Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas
| | - Jorge Wong
- Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas
| | - Karen H Lu
- Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Robert C Bast
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - John T McDevitt
- Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas.
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Bodelon C, Pfeiffer RM, Buys SS, Black A, Sherman ME. Analysis of serial ovarian volume measurements and incidence of ovarian cancer: implications for pathogenesis. J Natl Cancer Inst 2014; 106:dju262. [PMID: 25217774 DOI: 10.1093/jnci/dju262] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Accumulating evidence suggests that many ovarian cancers represent metastases from occult fallopian tube carcinomas or tumors arising within ovarian endometriosis. We hypothesized that small ovarian volumes, as reflected in nonvisualization by transvaginal ultrasound (TVU), would be a marker of lower ovarian cancer risk, whereas enlargement on serial examinations would indicate higher risk. METHODS To address these hypotheses, we analyzed serial ovarian volume measurements determined by TVU for 29321 women (102787 scans) performed in the ovarian cancer screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial. Cox models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of association between TVU results and ovarian cancer. We assessed whether increasing ovarian volume preceded diagnosis of ovarian cancer in a nested case-control analysis comparing case patients and control patients matched on age, center, and screening year (1:4 ratio). All statistical tests were two-sided. RESULTS Visualization of normal-appearing ovaries at the last TVU scan was associated with marginally higher ovarian cancer risk compared with nonvisualization of the ovaries (HR = 1.42, 95% CI = 1.00 to 2.01). Ovarian volume increased statistically significantly in ovarian cancer case patients one to two years before diagnosis (P < .001), but not in matched control patients. CONCLUSION Our analysis of TVU data suggests that increasing ovarian volume is associated with greater ovarian cancer risk, but it is only detectable one to two years before diagnosis.
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Affiliation(s)
- Clara Bodelon
- Division of Cancer Epidemiology and Genetics (CB, RMP, AB, MES) and Division of Cancer Prevention (MES), National Cancer Institute, Rockville, MD; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT (SSB).
| | - Ruth M Pfeiffer
- Division of Cancer Epidemiology and Genetics (CB, RMP, AB, MES) and Division of Cancer Prevention (MES), National Cancer Institute, Rockville, MD; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT (SSB)
| | - Saundra S Buys
- Division of Cancer Epidemiology and Genetics (CB, RMP, AB, MES) and Division of Cancer Prevention (MES), National Cancer Institute, Rockville, MD; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT (SSB)
| | - Amanda Black
- Division of Cancer Epidemiology and Genetics (CB, RMP, AB, MES) and Division of Cancer Prevention (MES), National Cancer Institute, Rockville, MD; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT (SSB)
| | - Mark E Sherman
- Division of Cancer Epidemiology and Genetics (CB, RMP, AB, MES) and Division of Cancer Prevention (MES), National Cancer Institute, Rockville, MD; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT (SSB)
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Cohen JG, White M, Cruz A, Farias-Eisner R. In 2014, can we do better than CA125 in the early detection of ovarian cancer? World J Biol Chem 2014; 5:286-300. [PMID: 25225597 PMCID: PMC4160523 DOI: 10.4331/wjbc.v5.i3.286] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 03/12/2014] [Accepted: 05/14/2014] [Indexed: 02/05/2023] Open
Abstract
Ovarian cancer is a lethal gynecologic malignancy with greater than 70% of women presenting with advanced stage disease. Despite new treatments, long term outcomes have not significantly changed in the past 30 years with the five-year overall survival remaining between 20% and 40% for stage III and IV disease. In contrast patients with stage I disease have a greater than 90% five-year overall survival. Detection of ovarian cancer at an early stage would likely have significant impact on mortality rate. Screening biomarkers discovered at the bench have not translated to success in clinical trials. Existing screening modalities have not demonstrated survival benefit in completed prospective trials. Advances in high throughput screening are making it possible to evaluate the development of ovarian cancer in ways never before imagined. Data in the form of human “-omes” including the proteome, genome, metabolome, and transcriptome are now available in various packaged forms. With the correct pooling of resources including prospective collection of patient specimens, integration of high throughput screening, and use of molecular heterogeneity in biomarker discovery, we are poised to make progress in ovarian cancer screening. This review will summarize current biomarkers, imaging, and multimodality screening strategies in the context of emerging technologies.
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Gilabert-Estelles J, Aghababyan C, Garcia P, Moscardo J, Royo S, Aniorte S, Gilabert-Aguilar J. Role of minimally invasive surgery in complex adnexal tumours and ovarian cancer. World J Obstet Gynecol 2014; 3:109-117. [DOI: 10.5317/wjog.v3.i3.109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Revised: 06/11/2014] [Accepted: 07/14/2014] [Indexed: 02/05/2023] Open
Abstract
Ovarian cancer is one of the most common causes of cancer-related death in women. Adnexal masses are frequently diagnosed during reproductive age and often require surgical removal. The risk of malignancy when dealing with a complex adnexal mass should be defined prior to surgery and several scoring systems may be useful for this purpose. Laparoscopic management of ovarian tumours allows a minimally invasive approach with respect to several oncological assumptions. In the last decade concerns have been raised regarding the risk of cyst rupture and tumour spillage as a consequence of the laparoscopic technique itself both in early and advanced stages of ovarian cancer. Although limited data have been reported in the literature on the use of minimally invasive techniques in ovarian cancer, the clear benefits of this approach must be balanced with the potential hazards in different clinical situations. Laparoscopic staging in borderline tumours and presumed early-stage ovarian cancer performed by a laparoscopic oncologist seems to be safe and effective when compared to laparotomy. The precise role of laparoscopy in patients with more advanced cancer is still to be defined, and the risk of suboptimal surgery should never outweigh the potential benefits of minimally invasive surgery. Thus, a tailored prediction of optimal laparoscopic debulking is mandatory in these patients.
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