Prof Manchanda presented at the 17th Annual Gynecologic Oncology Symposium on 8th November. The symposium was held by the Department of Gynecologic Oncology at Beijing Obstetrics and Gynecology Hospital, Capital Medical University.
Prof was invited to present on the topic ‘Mainstreaming genetic testing at cancer diagnosis’ to the our audience of Chinese gynecologists, PhDs, and Master’s students.
Professor Manchanda gave a talk at Future Dreams patient support group on our research studies for women’s cancer prevention. Future
We hosted two fantastic Patient and Public Involvement (PPI) workshops for the LEGACY project in February. We heard from 16
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, and 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.
This study investigated whether offering unselected genetic testing of a panel of BRCA1/BRCA2/PALB2 genes to everyone diagnosed with breast cancer was cost-effective compared to the current model of BRCA1/BRCA2 testing based on a patient’s family history/clinical criteria. This study found that unselected panel gene testing for everyone at breast cancer diagnosis was highly cost-effective compared to the current model of testing for UK and US health systems, and could save 2101 cases of ovarian and breast cancer in the UK, and 2406 in the US per year.
Value based genetic technology for breast cancer in China. (2020-2023)
This study investigated whether offering unselected genetic testing of a panel of BRCA1/BRCA2/PALB2 genes to everyone diagnosed with breast cancer was cost-effective compared to the current model of BRCA1/BRCA2 testing based on a patient’s family history/clinical criteria. This study found that unselected panel gene testing for everyone at breast cancer diagnosis was highly cost-effective compared to the current model of testing for UK and US health systems, and could save 2101 cases of ovarian and breast cancer in the UK, and 2406 in the US per year.
Value based genetic technology for breast cancer in China. (2020-2023)
A multicentre UK cohort questionnaire study to determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk.
We found that RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.
This study evaluated the cost-effectiveness of population-based BRCA testing in general population women across different countries/health systems. Our findings are split across high-income (HIC), upper-middle income (UMIC) and low-middle income countries (LMIC). Our findings suggest that population-based BRCA testing for countries evaluated is extremely cost-effective across high (US/UK/Netherlands) and upper/middle income countries’ health systems (China/Brazil), is cost-saving for high-income health systems from a societal perspective, and can prevent tens of thousands more breast or ovarian cancer cases.
We for the first time defined the precise ovarian cancer risk thresholds at which risk reducing salpingo oophorectomy (preventive surgery) should be undertaken for ovarian cancer prevention in both pre- and post-menopausal women.
Our findings show this is cost-effective in intermediate risk women too, saving 7-10 years of a woman’s life. This has significant implications for a number of women who currently can’t access risk reducing surgery. It also provides clinical utility for genetic testing of intermediate risk ovarian cancer genes. This has led to change in guidelines/practice for surgical prevention of ovarian cancer.
Value based genetic technology for breast cancer in China (2020-2023)
Investigating BRCAness in epithelial ovarian cancer (EOC) in India to develop stratified surgical and chemotherapy options (2017-2020)
Correlation of p53 IHC expression with TP53 mutation status in Endometrial Carcinoma (Co-investigator) (2017-2019)
UK FOCSS – UK Familial Ovarian Cancer Screening Study
UKCTOCS – UK Collaborative Trial of Ovarian Cancer Screening
ALDO – Avoiding late diagnosis of ovarian cancer
Shape Up following cancer treatment
SOCQER2
Use of Plasmajet in ultra-radical surgery for advanced Ovarian Cancer (2015-2019)
SURAKSHA- South Asian Breast Cancer Risk Prediction, Genetic testing & Health Management programme (2020-2021)
SHAPE
STATEC
MAPPING
ROCkeTS
SCCAN
GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V)
For more details on these support projects, click here!
PROTECTOR is a research study for women who are at an increased risk of developing ovarian cancer, due a strong family history of cancer, or an alteration in genes (such as BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, or PALB2). This study assesses the impact of surgery to remove the fallopian tubes and ovaries to prevent ovarian cancer.
Participants can choose whether to have no surgery, the usual operation to remove both tubes and ovaries, or a new 2-step approach of removing the fallopian tubes first followed by a second operation to remove the ovaries later.
The study assesses the impact of these surgeries on sexual function, hormone levels, quality of life and overall satisfaction. 41 sites across the UK are recruiting. PROTECTOR is funded by Barts Charity & Rosetrees Trust.
PROTECTOR Phase 1 has completed recruitment, and we are looking to open for Phase 2 in January 2025.
DETECT-2 is a study investigating if genetic testing can be offered to people in their own home.
In this study, participants who have been diagnosed with ovarian, womb, or bowel cancer are randomly assigned to be offered either conventional genetic testing by their cancer team or genetic testing at home. This new model is called “direct-to-patient” testing and includes offering genetic testing information on an interactive app or website, and offering genetic testing by a home saliva kit posted to participants.
DETECT-2 will assess if direct-to-patient genetic testing impacts participants’ willingness to accept genetic testing, or has an impact on their quality-of-life, satisfaction, or mental wellbeing. It will also assess if direct-to-patient testing is cost-effective.
DETECT-2 is supported by GSK and the North East London Cancer Alliance
PROTECT-C is offering genetic testing to women (women, trans men and non-binary people with female reproductive organs) to see if they have an increased risk of breast, ovary, bowel and/or womb cancer. This is regardless of whether they or their families have had cancer.
Specially trained counsellors are available through a helpline (telephone, virtual, email). If a participant decides to proceed with genetic testing, they will be sent a saliva kit for genetic testing at home (a “direct-to-patient” approach).
PROTECT-C aims to find out how many women decide to have genetic testing, their experience, and how this affects their quality of life, satisfaction and mental well-being.
PROTECT-C will assess the number of people identified to be at increased risk, and how many of them take up screening and prevention options. The study will also assess whether it is cost-effective for the NHS to offer genetic testing to all women in the population.
PROTECT-C is funded by a £3.89 million research grant from Yorkshire Cancer Research, and is aiming to launch in 2025.
For more information please visit: https://protect-c.co.uk
This project aims to review the status of BRCA awareness, community support and BRCA testing provision, experience and satisfaction in the ‘at-increased-risk’ Jewish community in the UK.
The review will focus on hereditary cancers associated with BRCA1 and BRCA2 gene mutations. It will concentrate on the provision of BRCA information and testing in the UK and also look at BRCA-related activities in Jewish communities internationally.
Delivery of the research will be carried out by researchers based at Queen Mary University of London in partnership with the JHCR project director, and under the guidance of expert advisors.
Research outcomes will help identify priority needs and recommendations to improve BRCA awareness in, and access to responsible BRCA testing for, the UK Jewish community.
Findings will be published in a community report and scientific papers – raising awareness and promoting positive action to improve hereditary cancer management and prevention in the UK Jewish community.
Ovarian cancer is typically diagnosed at a late stage which is associated with a worse prognosis. There are also no effective screening tests available for ovarian cancer.
OVACATCH aims to improve earlier diagnosis of ovarian cancer or identify cancers that current investigations may miss, by using longitudinal multiple biomarker algorithms derived from serum blood tests.
These will be validated using prospectively collected longitudinal serum samples held in biobanks from women with cancer diagnoses and healthy controls. A prospective cohort screening trial will then be conducted to evaluate these multi-marker algorithms compared to current methods of ovarian cancer surveillance using ROCA (Risk of Ovarian Cancer Algorithm).
OVACATCH will evaluate false positive rate, feasibility, compliances, satisfaction and anxiety with screening. This will provide the initial data needed to design a large multicentre screening trial for ovarian cancer, moving the needle forward towards developing an effective screening strategy for ovarian cancer.
The current literature around risk of serous endometrial cancer in BRCA pathogenic variant (PV) carriers is equivocal. There have been few studies that have stratified the risk in serous endometrial cancers and none focusing specifically on this histopathological subtype of endometrial cancer.
There have been no case-control studies to address this issue and the cohort studies demonstrating increased risk report large confidence intervals, while some others found no increase in risk. The true prevalence of BRCA1/BRCA2 PVs in prospective unselected UK serous EC patients is unknown. There remains continued uncertainty around whether BRCA1 PV carriers should undergo preventive hysterectomy (or not).
This study will address knowledge gaps such as the risk of serous endometrial cancer in patients with BRCA1/BRCA2 PVs, if hysterectomy would be cost-effective in the UK for BRCA1 and BRCA2 PV carriers, and if hysterectomy is acceptable alongside risk-reducing salpingo-oophorectomy for these carriers.
UKCOGS is a national study into the changes in diagnosis and treatment of gynaecological oncology patients that occurred in response to COVID-19. It aims to understand the decisions made by multi-disciplinary teams working in gynaecological oncology hospitals, the changes that occurred in these hospitals, and the impact of these changes on the health and survival of cancer patients.
The study is endorsed and supported by the British Gynaecological Cancer Society, Royal College of Obstetricians and Gynaecologists, NCRI Gynaecological Cancer Clinical Studies Group, British Association of Gynaecological Pathologists, and charities including Ovacome, The Eve Appeal, Target Ovarian Cancer, Ovarian Cancer Action, Jo’s Cervical Cancer trust and GO Girls.
For more information please visit: https://www.bgcs.org.uk/professionals/covid19-resources/research-studies/
Genetic testing in ovarian cancer patients is now being implemented across the NHS. It’s hoped that by doing this, patients across the NHS will have even better treatments and that in some families, cancers will be prevented. This trial offers a genetic test to women with certain types of ovarian cancer. This is to detect gene alterations that may be a cause of ovarian cancer.
In this study we aim to find out more about:
We also want to investigate the factors that affect the risk of developing ovarian cancer. This includes looking at how gene changes and other factors that might affect:
SIGNPOST entails collecting samples including cancer, blood, and genetic information.
The study is open to women who:
For more information please visit: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-genetic-testing-for-ovarian-cancer-signpost
The team has conducted a service evaluation of the BRCA-DIRECT pathway to assess the impact of implementing unselected genetic testing at the point of breast cancer diagnosis in London.
This evaluation encompassed clinical service performance, cost-effectiveness modelling, and patient satisfaction.
We have preliminary data we have presented recently at the BGCS Annual Scientific Meeting, and are working towards disseminating these results soon.
For more information please visit J-BRCA (nhsjewishbrcaprogramme.org.uk)
For more information please visit https://learninghub.nhs.uk/catalogue/ec-lynch-testing/about
Now that we have identified the lifetime risk threshold of breast cancer at which a risk-reducing mastectomy (RRM) would be cost-effective, it is important prior to clinical implementation to evaluate the acceptability of this risk-reducing strategy.
We will be undertaking a vignette study and randomising general population women into 5 groups with different lifetime risks of breast cancer, and asking a series of questions on acceptability of RRM.
Previous studies have analyzed complications and menopausal symptoms of opportunistic salpingectomy (removing the fallopian tubes during other gynecological surgeries), but so far have not evaluated the age of menopause – an important factor because early menopause can have negative consequences for bone health, the cardiovascular system, sexual health and cognitive function.
We will analyze blood samples from participants in the HOPPSA study, where 2,700 women have undergone hysterectomy with or without opportunistic salpingectomy. They are offered to provide blood samples on two occasions: 1–8 and 2–9 years after the operation. In this way, we can compare the age of menopause between those who have undergone opportunistic salpingectomy and those who have not.
This project will evaluate the cost-effectiveness of colorectal cancer surveillance for people in the UK with Lynch syndrome, in collaboration with teams at St Mark’s Hospital and Amsterdam University Medical Center (UMC).
Using retrospective, patient-level colonoscopy records and established colorectal cancer simulation models adapted for Lynch syndrome, we will estimate the costs and health outcomes of alternative surveillance schedules. Results may help quantify the potential benefits of identifying Lynch syndrome via genetic testing and inform future policy and guideline development for colorectal cancer prevention in this population.
