UK Familial Ovarian Cancer Screening Study (UK FOCSS)

Overview

Up to 10% of ovarian cancers can be attributed to an inherited genetic predisposition.  Women at high risk of developing the disease can be identified from their family history of cancer, where certain types of cancer are seen in affected relatives (e.g. ovarian cancer, breast cancer).  Currently, the only strategy available to reduce the risk of developing ovarian cancer is surgery to remove the ovaries and fallopian tubes. However, many women are unwilling to undergo risk-reducing surgery.  The aim of this national study is to find out whether screening tests can pick up ovarian cancer at an early stage, when treatment is more likely to be successful.

UK FOCSS Centres

centres


ISRCTN No - 32794457
UK CRN ID - 1069
Patient Information Sheet - Download

Design/ Intervention

Prospective single arm screening study. 

  • Screening with 4-monthly serum CA125 and annual transvaginal ultrasound scan of the ovaries. 
  • Collection of serial blood samples three times a year for retrospective analysis with novel tumour markers.

Objectives/ Aims

Objective 1

  • To develop an optimised screening strategy for ovarian cancer in terms of the most appropriate screening tests, criteria for interpretation of results, screening interval, morbidity and cost in women at high risk because of a strong family history or inherited genetic predisposition.

Objective 2

  • To establish a serum bank for future assessment of novel tumour markers.

Primary Outcome

Sensitivity, Specificity and Positive Predictive Value of the UKFOCSS screening strategy for the detection of primary epithelial ovarian and fallopian tube cancer.

Subjects

Phase 1 3563 women

Phase 2 4531 women

Inclusion/Exclusion Criteria

Inclusion Criteria Eligibility is determined as follows:
The volunteer should either have been affected by one of the following cancers or be a first degree relative (FDR) of an affected family member.  (Tubal and primary peritoneal cancers may be considered equivalent to ovarian cancer.)

Families with ovarian or ovarian & breast cancer

  • ≥2 individuals with ovarian cancer who are FDR
  • One ovarian cancer and 1 breast cancer <50 years who are FDR
  • One ovarian cancer and 2 breast cancers < 60 years who are FDR
  • Breast cancer in volunteer/ proband (≤45 years) and mother with both breast and ovarian cancer (in the same person)
  • Breast cancer in volunteer/ proband (≤40 years) and sister with both breast and ovarian cancer (in the same person)
  • Criteria 1, 2, and 3 (above) can be modified where paternal transmission is occurring i.e. families where affected relatives are related by second degree through an unaffected intervening male relative and there is an affected sister are eligible.

Families with a known gene mutation

  • The family contains an affected individual with a mutation of one of the known OC predisposing genes, e.g. BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS1 and PMS2.

Families with colorectal cancer (HNPCC or Lynch syndrome)

  • The family contains ≥3 individuals with a HNPCC related cancer*, who are FDR and  ≥1 case is diagnosed before 50 years and the cancers affect ≥1 generation*HNPCC related cancers - colorectal, endometrial, small bowel, uretic and renal pelvic cancers

Families with only breast cancer*

  • ≥4 breast cancers
  • 3 breast cancers related by FDR

    1. one ≤30 years or
    2. all ≤40 years or
    3. one MBC (Male Breast Cancer) and one b/l breast cancer
  • Breast cancer in volunteer/ proband (≤50 years) and

    1. breast cancer in mother (age of onset being ≤30 years in one and ≤50 years in the other) or
    2. b/l breast cancer in mother (≤40 years onset) or
    3. one MBC and one b/l breast cancer
  • Two MBC (one <40 years) in the family and proband is a FDR of one of them

Families with Ashkenazi Jewish ethnicity (additional criteria)*

AJ ethnicity and any one of the following:

  • Breast cancer (<40 years) or bilateral breast cancer (first cancer <50 years) in volunteer/ proband, irrespective of FH (family history) of cancer
  • Breast cancer in volunteer/ proband (<50 years) and one FDR with breast cancer (<50years) or ovarian cancer (any age) or MBC (any age)
  • Breast cancer in volunteer/ proband (<60 years) and one FDR with breast cancer (<40 years) or ovarian cancer (any age) or MBC (any age)
  • One FDR with ovarian cancer (<50 years)
  • FDR with breast and ovarian cancer in the same woman (any age)
  • Two FDR with breast cancer (<40 years)
  • Two MBC (<60 years) in the family and proband is a FDR of one of them

*Families in these categories negative on full BRCA1 and BRCA2 screening are ineligible.

Exclusion Criteria
  • Past history of bilateral oophorectomy (women with one or both fallopian tubes still present are eligible)
  • Age <35 years
  • Women participating in other ovarian cancer research trials


Definition of Ovarian Cancer’
For the purposes of determining a woman’s eligibility based on the occurrence of ovarian cancer in her family history, the term ‘ovarian cancer’ specifically refers to ‘epithelial ovarian cancer’ and does not include ‘borderline ovarian tumour’.

Recruitment

Eligible women were recruited via Clinical Genetics centres or collaborating medical departments (e.g. gynaecology, medical oncology).

Study Duration

May 2002 – March 2012

Bio Bank

Serum, plasma and DNA samples

  • Blood samples from 5024 donors: 38708 serial serum samples, 34355 serial plasma samples
  • DNA samples from 3935 donors: 3935 DNA samples

Investigators

Prof Ian Jacobs Chief Investigator
(UCL, University of Manchester)
Prof Usha Menon Co-Investigator
(UCL)
Dr James Mackay Co-Investigator
(UCL)
Dr Steve Skates Co-Investigator
(Harvard Medical School)
Dr Adam Rosenthal
Co-Investigator
(Clinical Lead) (Barts Cancer Institute)

Research Team

Lindsay Fraser Senior Research Associate, Trial Manager
Ms Sue Philpott
Senior Research Nurse, Data Manager, Safety Officer
Dr Ranjit Manchanda
Subspecialty Fellow
Dr Andy Ryan
Senior Data Manager
Mr Robert Liston
Senior Software Analyst
Dr Matthew Burnell
Statistician
Jessica Mozersky
Trial Manager
Lisa Perrault
Trial Coordinator, Data Manager
Philip Badman
Trial Coordinator, Data Manager, Safety Officer
Michele Johnson
Research Nurse
Kathryn Harris
Research Assistant
Dr Richard Hadwin
Subspecialty Fellow
Lanre Odunlami
Software Analyst

Administration Team

Lisa Hinton
Administrator
Agata Chrzanowska
Administrator
Lesley Hague
Administrator
Tracy Pearmain
Administrator

Laboratory Team

Jeremy Ford
Laboratory Manager
Richard Gnu
Bio Medical Scientist
Nuno Alvez
Medical Laboratory Assistant
Josie Cunningham
Medical Laboratory Assistant
Kristin Tamm
Medical Laboratory Assistant

Data Monitoring Committee

Prof Max Parmar (Chair) Head, Cancer Division, MRC Clinical Trials Unit, London
Dr Shehla Mohammed Consultant Clinical Geneticist and Head of Service for the Regional Genetics Centre, Clinical Genetics, Guy’s Hospital, London
Ms Karina Reynolds Consultant Gynaecological Oncologist, Barts and The London, Gynaecological Cancer Centre

Trial Steering Committee

Dame Prof Julietta Patnick (Chair) Director NHS Cancer Screening Programmes
Prof Diana Eccles Professor of Cancer Genetics at the University of Southampton and Director of the University of Southampton Clinical Trials Unit
Prof Stephen Duffy Professor of Cancer Screening, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine
Mr Derek Cruikshank Consultant Gynaecological Oncologist, Clinical Director of Gynaecology, The James Cook University Hospital, Middlesbrough
Louise Bayne Chief Executive, Ovacome

Trial Management Committee

Prof Ian Jacobs (Chair) Professor of Gynaecological Cancer , Vice-President and Dean of the Faculty of Medical and Human Sciences, University of Manchester
Prof Usha Menon Professor of Gynaecological Cancer, UCL Institute for Women’s Health
Dr James Mackay Consultant Clinical Genetic Oncologist, UCL
Dr Steven Skates Associate Professor, Department of Medicine, Harvard Medical School, Boston
Dr Adam Rosenthal Senior Lecturer/Consultant Gynaecological Oncologist, Barts Cancer Institute
Lindsay Fraser Senior Research Associate, UCL

Outcome Review Committee

Dr Liz Benjamin Pathologist, UCLH NHS Trust
Dr Naveena Singh Pathologist, Barts Health NHS Trust
Dr Adam Rosenthal Gynae-Oncologist, Barts Health NHS Trust
Sue Philpott Senior Research Nurse, UCL

Ethics Committee

NRES Committee Cambridge South REC Ref 97/5/007

Centres

Belfast
Belfast City Hospital

Mr Hans Nagar (PI),  Adrina O’Donnell, Rachel Hardy (Centre Contact)
Birmingham
Birmingham City Hospital

Mr James Nevin (PI), Brian Gammon (Centre Contact)

Bristol
St Michael’s Hospital

Mr Bob Anderson (PI), Carole Shahin (Centre Contact)
Cambridge
Addenbrooke’s Hospital

Mr Robin Crawford (PI), Barbara Newcombe (Centre Contact)
Cardiff
Cardiff University Hospital

Mr Mark Rogers (PI), Sarah Scourfield (Centre Contact)
Cheltenham & Gloucester
Cheltenham General Hospital

Mr Rob Gornall (PI), Kate Trigg-Hogarth (Centre Contact)
Chester
Countess of Chester Hospital

Sharon Rowe (PI), Mary Aldous (Centre Contact)
Cumberland
Cumberland Infirmary

Dr Sheila Pearson (PI), Angela Brit (Centre Contact)

Derby
Derby City General Hospital

Mr Howard Jenkins (PI), Samantha Crockett (Centre Contact)
Durham
University Hospital of North Durham

Dr Partha Sengupta (PI), Jean Dent (Centre Contact)

Edinburgh

Western General Hospital

Dr Mary Porteous (PI), Susan MacKenzie (Centre Contact)

Essex-Mid

St John's Hospital

Mr Colin Partington (PI), Fay Munson (Centre Contact)

Gateshead

Queen Elizabeth Hospital

Mr Richard Edmondson (PI), Lillian Lee (Centre Contact)

Glasgow

Yorkhill Hospital

Dr Rosemary Davidson (PI), Lesley Snadden, Sarah Gibson (Centre Contact)

Hull

Hull Royal Infirmary

Prof Mike Lind (PI), Jane Smales (Centre Contact)

Kettering

Kettering General Hospital

Mr Robert Haughney (PI), Joanne Walsh (Centre Contact)

Kent, East

Queen Elizabeth the Queen Mother Hospital

Mr Andy Nordin (PI), Lin Tunkara (Centre Contact)

Kent, West

Maidstone Hospital

Mr Andreas Papadopoulos (PI), Sandra Burt (Centre Contact)

Leeds

St James’s Hospital Leeds

Dr Carol Chu (PI), Emma O’Hara, Denise Hancock (Centre Contact)

Leicester

Leicester Royal Infirmary

Mr Quentin Davies (PI), Julia Walker, Judy Maynard-Mills (Centre Contact)

Lincoln

Lincoln County Hospital

Mr Martin Lamb (PI), Olesya Francis (Centre Contact)

Liverpool

Liverpool Women’s Hospital

Dr Carol Benjamin (PI), Carole Ballard (Centre Contact)

London, Hammersmith

Hammersmith Hospital

Ms Sadaf Ghaem-Maghami (PI)

London, North West

Kennedy Galton Centre

Mr Huw Dorkins (PI)

London, UCLH (Barts / Guys)

University College Hospital (Barts Hospital, Guy’s Hospital)

Prof Usha Menon (PI), Saz Chamberlain (Centre Contact)

London, St George’s

St George's Hospital

Dr Kevin Hayes (PI)

Manchester

St Mary’s Hospital

Prof Gareth Evans (PI), Karen Tricker (Centre Contact)

Middlesbrough

James Cook University Hospital

Dr Paul Brennan (PI), Gill Laidlaw (Centre Contact)

Milton Keynes

Milton Keynes General Hospital

Prof Christopher Lynch (PI), Heini Alderman (Centre Contact)

Northampton

Northampton General Hospital

Mr Alistair Duncan (PI), Nancy Hopewell (Centre Contact)

Nottingham

Nottingham City Hospital

Ms Karin Williamson (PI), Teresa Parkes (Centre Contact)

Oxford

Churchill Hospital

Dr Lisa Walker (PI), Denise Fleming Brown (Centre Contact)

Peninsula

Royal Devon and Exeter Hospital / Royal Cornwall Hospital

Dr Carole Brewer (PI Exeter / Cornwall), Linda Garcia, Jacky Stewart, Emma Kent / Philip Harvey, Katharine Hill (Centre Contact)

Derriford Hospital

Mr Tony Falconer (PI, Plymouth), Julie Pascoe (Centre Contact)

Royal Marsden

The Royal Marsden

Dr Rosalind Eeles (PI), Saz Chamberlain (Centre Contact)

Sheffield

Sheffield Children's Hospital

Dr Jackie Cook (PI), Cathryn Dow (Centre Contact)

Southampton

Princess Anne Hospital

Prof Diana Eccles (PI)

Staffordshire, North

North Staffordshire Royal Infirmary

Mr Vijay Menon (PI), Julie Robertson (Centre Contact)

Surrey

Frimley Park Hospital

Mr Gareth Beynon (PI), Susan Richmond (Centre Contact)

Stoke Mandeville

Stoke Mandeville Hospital

Mr Damien Eustace (PI), Tracey Stammers (Centre Contact)

Swansea

Singleton Hospital

Dr Alex Murray (PI), Wendy Jones, Liwsi Protheroe (Centre Contact)

Wales, North

Glan Clywd Hospital

Dr Alex Murray (PI), Julie Greer (Centre Contact)

Wycombe

Wycombe General Hospital

Mr Damien Eustace (PI), Emma Hogbin (Centre Contact)

Publications

Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Mozersky J, Hadwin R, Cafferty FH, Benjamin E, Singh N, Evans DG, Eccles DM, Skates SJ, Mackay J, Menon U & Jacobs IJ.  (2013).  Results of annual screening in phase 1 of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule.  J Clin. Oncol 31, 49-57.

Rosenthal AN (2012). Ovarian cancer screening in the high-risk population; the UK Familial Ovarian Cancer Screening Study (UKFOCSS). Int J Gynecol Cancer vol. 22 Suppl 1, S27-S28. 10.1097/IGC.0b013e318251cc3f

Conference Presentations

  • Philpott S, Fraser L, Manchanda R, Badman P, Skates SJ, Mackay J, Menon U, Jacobs IJ & Rosenthal AN.  Detection of non-ovarian cancers on Phase 2 of the UK Familial Ovarian Cancer Screening Study (UK FOCSS).  British Gynaecological Cancer Society Annual Meeting.  Belfast, Northern Ireland.  20-21 June 2013.  (Poster presentation)
  • Rosenthal AN.  UK FOCSS: What have we learnt so far?  British Gynaecological Cancer Society Annual Meeting.  Belfast, Northern Ireland.  20-21 June 2013.  (Invited Lecture)
  • Rosenthal AN, Fraser L, Philpott S, Manchanda R, Badman P, Hadwin R, Evans DG, Eccles DM, Skates SJ, Mackay J, Menon U & Jacobs IJ on behalf of the UK FOCSS collaborators.  Results of 4-monthly Screening in the UK Familial Ovarian Cancer Screening Study (UK FOCSS Phase 2).  Annual meeting of the American Society of Clinical Oncology, Chicago, USA.  May/June 2013.  (Oral presentation)
  • Philpott S, Fraser L, Manchanda R, Badman P, Skates SJ, Mackay J, Menon U, Jacobs IJ & Rosenthal AN.  Detection of non-ovarian cancers on Phase 2 of the UK Familial Ovarian Cancer Screening Study (UK FOCSS).  UCL Institute for Women’s Health 8th Annual Meeting, London, May 2013.  (Oral presentation)
  • Rosenthal AN, on behalf of the UK FOCSS Investigators and Collaborators.  Incidental diagnosis of endometrial cancer during high risk ovarian cancer screening.  British Gynaecological Cancer Society, London, July 2012.  (Poster presentation)
  • Rosenthal AN, on behalf of the UK FOCSS Investigators and Collaborators.  High Risk Population screening: The UK Familial Ovarian Cancer Screening Study (UK FOCSS)   4th International Conference on Ovarian Cancer Screening, London, United Kingdom, November 2011.  (Oral presentation)
  • Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Skates SJ, Mackay J, Menon U & Jacobs IJ.  UK FOCSS Phase 1 Screening.  British Gynaecological Cancer Society Annual Meeting, Dublin, Ireland, November 2009.  (Oral presentation)
  • Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Skates SJ, Mackay J, Menon U & Jacobs IJ.  UK FOCSS results of Phase 1 Annual Screening.  16th Annual Meeting of the European Society of Gynaecological Oncology, Belgrade, Serbia.  October 2009.  (Poster presentation)
  • Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Mozersky J, Hadwin R, Skates SJ, Mackay J, Menon U & Jacobs IJ.  UK FOCSS Phase 1 Screening.  15th Annual Meeting of the European Society of Gynaecological Oncology, Berlin, Germany, October-November 2007.  (Oral presentation)
  • Rosenthal AN, Fraser L, Badman P, Philpott S, Mozersky J, Skates SJ, Mackay J, Menon U & Jacobs IJ.  UK FOCSS Interim Results of Annual Screening.  14th Annual Meeting of the European Society of Gynaecological Oncology, Istanbul, Turkey, October-November 2005.  (Oral presentation)

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