Gynaecological Cancer Research Centre (2004 - 2018)

The core research interests of the group are early detection, risk factors and stratification, biomarker discovery and management of women at increased risk of gynaecological cancers especially ovarian.  

The trials and studies undertaken during 2004-2018 when the group were based at Institute for Women’s Health include:

Ongoing:

UKCTOCS - UK Collaborative Trial of Ovarian Cancer Screening (ukctocs.mrcctu.ucl.ac.uk)

The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was designed to test whether screening can help save lives by detecting the disease earlier. Between April 2001-Sept 2005, 202,638 postmenopausal women, aged 50-74 years were recruited through 13 trial centres in England, Wales and Northern Ireland. Women were randomly allocated to one of three groups (i) control (C ) - no screening (ii) multimodal screening - annual blood test for serum CA125 measurement. The results were interpreted using the ‘Risk of Ovarian Cancer Algorithm’, with transvaginal ultrasound as a second line test in case of abnormality (iii) ultrasound screening – annual and second line tests were transvaginal scans. 
The trial showed for the first time that multimodal screening results in the detection of significantly more early stage ovarian/tubal/peritoneal cancers than no screening. The reduction in mortality was not definitive at the first analysis. Longer term follow up is underway to confirm if screening can lives. Please visit the link above for more information.

Selected publications:

• Menon U, Gentry-Maharaj A, Ryan A, Sharma A, Burnell M, Hallett R, Lewis S, Lopez A, Godfrey K, Oram D, Herod J, Williamson K, Seif M, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso N, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Skates S, Parmar M, Jacobs I. Recruitment to multicentre trials--lessons from UKCTOCS: descriptive study. Bmj. 2008;337:a2079.
• Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, Davies S, Philpott S, Lopes A, Godfrey K, Oram D, Herod J, Williamson K, Seif M, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso N, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Singh N, Dawnay A, Skates S, Parmar M, Jacobs I. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). The lancet oncology, 2009. 10(4): p. 327-40.
• 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 J2, 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 Jun 20;33(18):2062-71. doi: 10.1200/JCO.2014.59.4945. Epub 2015 May 11.
• Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387(10022):945-56

UKLWC - UKCTOCS Longitudinal Women's Cohort (uklwc.mrcctu.ucl.ac.uk)

UKLWC is the biobank of samples and data donated by the participants of UKCTOCS (202,280 postmenopausal women from the general population in England, Wales and Northern Ireland). A large number of secondary research has been undertaken by many researchers both from UCL and more widely. These are detailed in the website above. As are how you could contact the team if you are a participant or a researcher.

UKOPS - UK Ovarian Cancer Population Study (ukops.mrcctu.ucl.ac.uk)

UKOPS was set up to answer 3 questions: identify a better/complimentary marker to CA125, identify genetic predisposition to ovarian cancer and identify symptoms for the disease. As part of the international Ovarian Cancer Association Consortium (OCAC), an amalgamation of over 75 groups from around the world, close to 40 low risk loci have been identified and further work to elucidate gene-environment interactions has been undertaken. In addition, the Ovarian Tumour Tissue Analysis (OTTA) has furthered the knowledge in molecular typing of different ovarian cancer histotypes. Over 100 publications have resulted from this effort.

Selected publications:

• Song H, Ramus SJ, Tyrer J, Bolton KL, Gentry-Maharaj A, Wozniak E, Anton-Culver H, Chang-Claude J, Cramer DW, DiCioccio R, Dork T, Goode EL, Goodman MT, Schildkraut JM, Sellers T, Baglietto L, Beckmann MW, Beesley J, Blaakaer J, Carney ME, Chanock S, Chen Z, Cunningham JM, Dicks E, Doherty JA, Durst M, Ekici AB, Fenstermacher D, Fridley BL, Giles G, Gore ME, De Vivo I, Hillemanns P, Hogdall C, Hogdall E, Iversen ES, Jacobs IJ, Jakubowska A, Li D, Lissowska J, Lubinski J, Lurie G, McGuire V, McLaughlin J, Medrek K, Moorman PG, Moysich K, Narod S, Phelan C, Pye C, Risch H, Runnebaum IB, Severi G, Southey M, Stram DO, Thiel FC, Terry KL, Tsai YY, Tworoger SS, Van Den Berg DJ, Vierkant RA, Wang-Gohrke S, Webb PM, Wilkens LR, Wu AH, Yang H, Brewster W, Ziogas A, Australian Cancer S, Australian Ovarian Cancer Study G, Ovarian Cancer Association C, Houlston R, Tomlinson I, Whittemore AS, Rossing MA, Ponder BA, Pearce CL, Ness RB, Menon U, Kjaer SK, Gronwald J, Garcia-Closas M, Fasching PA, Easton DF, Chenevix-Trench G, Berchuck A, Pharoah PD, Gayther SA. A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nature genetics. 2009;41(9):996-1000.
• Goode EL, Chenevix-Trench G, Song H, Ramus SJ, Notaridou M, Lawrenson K, Widschwendter M, Vierkant RA, Larson MC, Kjaer SK, Birrer MJ, Berchuck A, Schildkraut J, Tomlinson I, Kiemeney LA, Cook LS, Gronwald J, Garcia-Closas M, Gore ME, Campbell I, Whittemore AS, Sutphen R, Phelan C, Anton-Culver H, Pearce CL, Lambrechts D, Rossing MA, Chang-Claude J, Moysich KB, Goodman MT, Dork T, Nevanlinna H, Ness RB, Rafnar T, Hogdall C, Hogdall E, Fridley BL, Cunningham JM, Sieh W, McGuire V, Godwin AK, Cramer DW, Hernandez D, Levine D, Lu K, Iversen ES, Palmieri RT, Houlston R, van Altena AM, Aben KK, Massuger LF, Brooks-Wilson A, Kelemen LE, Le ND, Jakubowska A, Lubinski J, Medrek K, Stafford A, Easton DF, Tyrer J, Bolton KL, Harrington P, Eccles D, Chen A, Molina AN, Davila BN, Arango H, Tsai YY, Chen Z, Risch HA, McLaughlin J, Narod SA, Ziogas A, Brewster W, Gentry-Maharaj A, Menon U, Wu AH, Stram DO, Pike MC, Wellcome Trust Case-Control C, Beesley J, Webb PM, Australian Cancer S, Australian Ovarian Cancer Study G, Ovarian Cancer Association C, Chen X, Ekici AB, Thiel FC, Beckmann MW, Yang H, Wentzensen N, Lissowska J, Fasching PA, Despierre E, Amant F, Vergote I, Doherty J, Hein R, Wang-Gohrke S, Lurie G, Carney ME, Thompson PJ, Runnebaum I, Hillemanns P, Durst M, Antonenkova N, Bogdanova N, Leminen A, Butzow R, Heikkinen T, Stefansson K, Sulem P, Besenbacher S, Sellers TA, Gayther SA, Pharoah PD, Ovarian Cancer Association C. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nature genetics. 2010;42(10):874-9.
• Timms JF, Cramer R, Camuzeaux S, Tiss A, Smith C, Burford B, Nouretdinov I, Devetyarov D, Gentry-Maharaj A, Ford J, Luo Z, Gammerman A, Menon U, Jacobs I. Peptides generated ex vivo from serum proteins by tumor-specific exopeptidases are not useful biomarkers in ovarian cancer. Clinical chemistry. 2010;56(2):262-71.
• Balogun N, Gentry-Maharaj A, Wozniak EL, Lim A, Ryan A, Ramus SJ, Ford J, Burnell M, Widschwendter M, Gessler SF, Gayther SA, Jacobs IJ, Menon U. Recruitment of newly diagnosed ovarian cancer patients proved challenging in a multicentre biobanking study. Journal of clinical epidemiology. 2011;64(5):525-30.
• Lim AW, Mesher D, Gentry-Maharaj A, Balogun N, Jacobs I, Menon U, Sasieni P. Predictive value of symptoms for ovarian cancer: comparison of symptoms reported by questionnaire, interview, and general practitioner notes. Journal of the National Cancer Institute. 2012;104(2):114-24.

Completed: 

UK FOCSS - UK Familial Ovarian Cancer Screening Study

Between June 2007 and May 2012, 4,348 women with an estimated lifetime OC risk of ≥ 10% who were unwilling to undergo risk-reducing surgery, were recruited at 42 NHS hospitals. They underwent 4-monthly multimodal screening with serum CA125 interpreted using ROCA and transvaginal ultrasound. Physician review was scheduled based on risk estimates. Through-out there were regular discussions about the effectiveness of surgery, Women were then followed up for a median of 4 years.
There was a clinically meaningful and significant down staging and higher rates of primary surgery in women being diagnosed with invasive epithelial ovarian cancer during screening in comparison to one year after the end of screening.  The performance characteristics of the screening strategy was encouraging and compliance was high.

Selected publications:

• Rosenthal AN, Fraser LSM, Philpott S, Manchanda R, Burnell M, Badman P, Hadwin R, Rizzuto I, Benjamin E, Singh N, Evans DG, Eccles DM, Ryan A, Liston R, Dawnay A, Ford J, Gunu R, Mackay J, Skates SJ, Menon U, Jacobs IJ; United Kingdom Familial Ovarian Cancer Screening Study collaborators. Evidence of Stage Shift in Women Diagnosed With Ovarian Cancer During Phase II of the United Kingdom Familial Ovarian Cancer Screening Study. J Clin Oncol. 2017 May 1;35(13):1411-1420. doi: 10.1200/JCO.2016.69.9330. Epub 2017 Feb 27.
• 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. Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol. 2013 Jan 1;31(1):49-57. doi: 10.1200/JCO.2011.39.7638. Epub 2012 Dec 3.

For access to UKFOCSS data and samples please contact Prof. Usha Menon :: u.menon@ucl.ac.uk

GCaPPS - Genetic Cancer Prediction through Population Screening

Following pre-test counselling and informed consent, 1034 Ashkenazi Jewish men and women were randomised to either population based or clinical criteria (family history) based genetic testing for BRCA founder mutations. Participants were followed up for three years after the test result. The study showed that compared to family-history based testing, population-based BRCA founder mutation testing doesn’t harm psychological health (anxiety, depression, health anxiety, distress, uncertainty)  or quality-of-life and identifies 150% additional BRCA carriers. Overall anxiety decreased with time. Long term follow up data shows a reduction in anxiety with population testing compared to family-history or clinical criteria based testing. We found, BRCA testing in the Jewish population is acceptable, feasible, can be undertaken in a community setting. It had high acceptability and was associated with 88% uptake and high satisfaction rates of ~95%. In a non-inferiority cluster-randomised trial we found that DVD-assisted pre-test counselling for population BRCA-testing is an effective, acceptable, non-inferior, time-saving and cost-efficient alternative to traditional genetic-counselling.

Our cost-effectiveness analysis shows, a population-based BRCA testing approach in the Ashkenazi Jewish population, reduces breast and ovarian cancer incidence, leading to up to an additional 33 days gain in life-expectancy and is extremely cost-effective (cost saving) with a discounted incremental cost-effectiveness ratio (ICER) = -£2960/quality adjusted life year (QALY). Probabilistic sensitivity analysis shows this remains cost-effective for 95% simulations at the £20,000/QALY NICE threshold. Our modelling suggests this could lead to 276 fewer ovarian and 508 fewer breast cancer cases in the UK. Overall, reduction in treatment costs could lead to a discounted cost savings of £3.7 million for the NHS.

Publications:

• Manchanda, R. et al. Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: a randomized controlled trial. J Natl Cancer Inst 107, 379, doi:10.1093/jnci/dju379 (2015).
• Manchanda, R. et al. Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population. J Med Genet, doi:10.1136/jmedgenet-2017-105195 (2018).
• Manchanda, R. et al. Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations. J Med Genet 53, 472-480, doi:10.1136/jmedgenet-2015-103740 (2016).
• Manchanda, R. et al. Attitude towards and factors affecting uptake of population-based BRCA testing in the Ashkenazi Jewish population: a cohort study. Bjog 126, 784-794, doi:10.1111/1471-0528.15654 (2019).
• Manchanda, R. et al. Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes. Bjog, doi:10.1111/1471-0528.15905 (2019).
• Manchanda, R. et al. Cost-effectiveness of population screening for BRCA mutations in Ashkenazi jewish women compared with family history-based testing. J Natl Cancer Inst 107, 380, doi:10.1093/jnci/dju380 (2015).
• Manchanda, R. et al. Cost-effectiveness of population based BRCA testing with varying Ashkenazi Jewish ancestry. Am J Obstet Gynecol 217, 578 e571-578 e512, doi:10.1016/j.ajog.2017.06.038 (2017).
• Patel, S. et al. Cost effectiveness of population based BRCA1 founder mutation testing in Sephardi Jewish women. Am J Obstet Gynecol 218, 431 e431-431 e412, doi:10.1016/j.ajog.2017.12.221 (2018).

UKGOSOC - UK Gynaecological Oncology Surgical Outcomes and Complications

UKGOSOC was a prospective audit of complications of major oncology surgery. It was undertaken at 10 gynaecological oncology centres in the UK and included web based data collection on 3000 procedures. It developed benchmarking standards for UK gynaecological oncology centres, established that risk-adjusted complication rates allows fairer institutional comparison and that hospital under-reporting is common for postoperative complications and hence use of patient-reported outcomes is important.

Publications:

• M Burnell  R Iyer  A Gentry-Maharaj  A Nordin  R Liston  R Manchanda  N Das  R Gornall  A Beardmore‐Gray  K Hillaby  S Leeson  A Linder  A Lopes  D Meechan  T Mould et al. Benchmarking of surgical complications in gynaecological oncology: prospective multicentre study. BJOG. 2016 Dec;123(13):2171-2180. doi: 10.1111/1471-0528.13994. Epub 2016 Mar 22.
• R Iyer, A Gentry-Maharaj, A Nordin, M Burnell, R Liston, R Manchanda, N Das, R Desai, R Gornall, A Beardmore-Gray, J Nevin, K Hillaby, S Leeson, A Linder, A Lopes, D Meechan, T Mould, S Varkey, A Olaitan, B Rufford, A Ryan, S Shanbhag, A Thackeray, N Wood, K Reynolds, and U Menon*. Predictors of complications in gynaecological oncological surgery: a prospective multicentre study (UKGOSOC—UK gynaecological oncology surgical outcomes and complications). Br J Cancer. 2015 Feb 3; 112(3): 475–484. Published online 2014 Dec 23. doi: 10.1038/bjc.2014.630
• R Iyer, A Gentry-Maharaj, A Nordin, R Liston, M Burnell, N Das, R Desai, R Gornall, A Beardmore-Gray, K Hillaby, S Leeson, A Linder, A Lopes, D Meechan, T Mould, J Nevin, A Olaitan, B Rufford, A Ryan, S Shanbhag, A Thackeray, N Wood, K Reynolds, and U Menon*.  Patient-reporting improves estimates of postoperative complication rates: a prospective cohort study in gynaecological oncology. Br J Cancer. 2013 Aug 6; 109(3): 623–632. Published online 2013 Jul 11. doi: 10.1038/bjc.2013.366

ICBP Module 4 - International Cancer Benchmarking Partnership

The ICBP is a partnership between England, Australia, Canada, Denmark, Northern Ireland, Norway, Sweden and Wales co-ordinated by the Department of Health (DH) in England with support from Cancer Research UK. Module 4 of the ICBP is an international survey on time intervals from onset of symptoms to commencement of treatment in newly diagnosed patients with lung, colorectal, breast, or ovarian cancer. A total of 14 664 eligible patients with CRC diagnosed between 2013 and 2015 were identified, of which 2866 were included in the analyses. It has demonstrated important differences in time intervals between 10 jurisdictions internationally in the four cancers. Previous findings that some cancers may progress even within the relatively short time frame supports the current emphasis on expediting diagnosis of cancer in patients presenting with symptoms.

Publications:

• Tørring ML, Falborg AZ, Jensen H, Neal RD, Weller D, Reguilon I; ICBP Working  Group, Menon U, Vedsted P. Advanced-stage cancer and time to diagnosis: An International Cancer Benchmarking Partnership (ICBP) cross-sectional study. Eur J Cancer Care (Engl). 2019 Sep;28(5):e13100. doi: 10.1111/ecc.13100. Epub 2019 May 22. PubMed PMID: 31119836.
• Weller D, Menon U, Zalounina Falborg A, Jensen H, Barisic A, Knudsen AK, Bergin RJ, Brewster DH, Cairnduff V, Gavin AT, Grunfeld E, Harland E, Lambe M, Law RJ, Lin Y, Malmberg M, Turner D, Neal RD, White V, Harrison S, Reguilon I; ICBP Module 4 Working Group, Vedsted P. Diagnostic routes and time intervals for  patients with colorectal cancer in 10 international jurisdictions; findings from  a cross-sectional study from the International Cancer Benchmarking Partnership (ICBP). BMJ Open. 2018 Nov 27;8(11):e023870. doi: 10.1136/bmjopen-2018-023870. PubMed PMID: 30482749; PubMed Central PMCID: PMC6278806. 
• Weller D, Vedsted P, Anandan C, Zalounina A, Fourkala EO, Desai R, Liston W, Jensen H, Barisic A, Gavin A, Grunfeld E, Lambe M, Law RJ, Malmberg M, Neal RD, Kalsi J, Turner D, White V, Bomb M, Menon U; ICBP Module 4 Working Group*. An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership: survey development and implementation. BMJ Open. 2016 Jul 25;6(7):e009641. doi: 10.1136/bmjopen-2015-009641. PubMed PMID: 27456325; PubMed Central PMCID: PMC4964239.

Research students