Quality of Life after Risk-Reducing Hysterectomy for Endometrial Cancer Prevention: A Systematic Review

BACKGROUND: Risk-reducing hysterectomy (RRH) is the gold-standard prevention for endometrial cancer (EC). Knowledge of the impact on quality-of-life (QoL) is crucial for decision-making. This systematic review aims to summarise the evidence. Methods: We searched major databases until July 2022 (CRD42022347631). Given the paucity of data on RRH, we also included hysterectomy as treatment for benign disease. We used validated quality-assessment tools, and performed qualitative synthesis of QoL outcomes. RESULTS: Four studies (64 patients) reported on RRH, 25 studies (1268 patients) on hysterectomy as treatment for uterine bleeding. There was moderate risk-of-bias in many studies. Following RRH, three qualitative studies found substantially lowered cancer-worry, with no decision-regret. Oophorectomy (for ovarian cancer prevention) severely impaired menopause-specific QoL and sexual-function, particularly without hormone-replacement. Quantitative studies supported these results, finding low distress and generally high satisfaction. Hysterectomy as treatment of bleeding improved QoL, resulted in high satisfaction, and no change or improvements in sexual and urinary function, although small numbers reported worsening. CONCLUSIONS: There is very limited evidence on QoL after RRH. Whilst there are benefits, most adverse consequences arise from oophorectomy. Benign hysterectomy allows for some limited comparison; however, more research is needed for outcomes in the population of women at increased EC-risk

Quality of life after risk-reducing surgery for breast and ovarian cancer prevention: a systematic review and meta-analysis

OBJECTIVE: To assess the impact of risk-reducing surgery (RRS) for breast cancer (BC) and ovarian cancer (OC) prevention on quality-of-life (QoL). We consider risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), and risk-reducing early-salpingectomy and delayed-oophorectomy (RRESDO). DATA SOURCES: We followed a prospective protocol (PROSPERO: CRD42022319782) and searched MEDLINE, EMBASE, PubMed, and Cochrane Library from inception to February 2023. STUDY ELIGIBILITY CRITERIA: We followed a PICOS framework. The population included women at increased risk of BC or OC. We focused on studies reporting QoL outcomes (health-related QoL (HRQoL), sexual function, menopause symptoms, body image, cancer-related distress or worry, anxiety or depression) after RRS, including RRM for BC and RRSO or RRESDO for OC. STUDY APPRAISAL AND SYNTHESIS METHODS: We used the Methodological Index for Non-Randomized Studies (MINORS) for study appraisal. Qualitative synthesis and fixed-effects meta-analysis was performed. RESULTS: Thirty-four studies were included (RRM:16 studies, RRSO: 19 studies, RRESDO: 2 studies). HRQoL was unchanged or improved in 13/15 studies post-RRM (N=986) and 10/16 studies post-RRSO (N=1617), despite short-term deficits (N=96 post-RRM and N=459 post-RRSO). Sexual function (using Sexual Activity Questionnaire) was affected in 13/16 studies (N=1400) post-RRSO, in terms of decreased sexual pleasure (-1.21[-1.53,-0.89]; N=3070) and increased sexual discomfort (1.12[0.93,1.31]; N=1400). Hormone replacement therapy after pre-menopausal RRSO was associated with an increase (1.16[0.17,2.15]; N=291) in sexual pleasure and a decrease (-1.20[-1.75,-0.65]; N=157) in sexual discomfort. Sexual function was affected in 4/13 studies (N=147) post-RRM, but stable in 9/13 studies (N=799). Body image was unaffected in 7/13 studies (N=605) post-RRM, whereas 6/13 studies (N=391) reported worsening. Increased menopause symptoms were reported in 12/13 studies (N=1759) post-RRSO with a reduction (-1.96[-2.81,-1.10]; N=1745) in Functional Assessment of Cancer Therapy-Endocrine Subscale. Cancer-related distress was unchanged or decreased in 5/5 studies post-RRM (N=365) and 8/10 studies post-RRSO (N=1223). RRESDO (2 studies, N=413) had better sexual function and menopause-specific QoL. CONCLUSION: RRS may be associated with QoL outcomes. RRM and RRSO reduce cancer-related distress, and do not affect HRQoL. Women and clinicians should be aware of body image problems post-RRM, together-with sexual dysfunction and menopause symptoms post-RRSO. RRESDO may be a promising alternative to mitigate QoL-related risks of RRSO

Impact of Multiple COVID-19 Waves on Gynaecological Cancer Services in the UK

Funding: This research was funded by the British Gynaecological Cancer Society (EMSG1L5R) and Ovacome charity. It is supported by the National Cancer Research Institute Gynaecological Cancer Clinical Studies Group and the British Association of Gynaecological Pathologists. The funding bodies had no role in the study design, data collection, analysis, interpretation or writing of the report, or decision to submit for publication. The research team was independent of funders. Acknowledgments: The study is supported by researchers at the Barts Cancer Research United Kingdom Centre for Excellence, Queen Mary University of London (C16420/A18066). We are grateful for the endorsement and support from charities and patient support groups such as Ovacome, The Eve Appeal, Target Ovarian Cancer, Ovarian Cancer Action, Jo’s Cervical Cancer Trust, and GO Girls. We are grateful for the support received from the Royal College of Obstetricians and Gynaecologists, the National Cancer Research Institute Gynaecological Cancer Clinical Studies Group, and the British Association of Gynaecological Pathologists.Peer reviewedPublisher PD

Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study

BACKGROUND:T1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting.METHODS:Healthy subjects (n = 102; mean age 41 years (range 17-83), male, n = 53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, lambda and extracellular volume fraction (ECV) in a core lab using standardized postprocessing.RESULTS:In healthy controls, mean native T1 values were 950 +/- 21 msec at 1.5 T and 1052 +/- 23 at 3 T. lambda and ECV values were 0.44 +/- 0.06 and 0.25 +/- 0.04 at 1.5 T, and 0.44 +/- 0.07 and 0.26 +/- 0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. lambda and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1.CONCLUSION:We show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites

Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

BRCA awareness and testing experience in the UK Jewish population:a qualitative study.

BACKGROUND: 1 in 40 UK Jewish individuals carry a pathogenic variant in BRCA1/BRCA2. Traditional testing criteria miss half of carriers, and so population genetic testing is being piloted for Jewish people in England. There has been no qualitative research into the factors influencing BRCA awareness and testing experience in this group. This study aimed to explore these and inform improvements for the implementation of population genetic testing. METHODS: Qualitative study of UK Jewish adults who have undergone BRCA testing. We conducted one-to-one semistructured interviews via telephone or video call using a predefined topic guide, until sufficient information power was reached. Interviews were audio-recorded, transcribed verbatim and interpreted using applied thematic analysis. RESULTS: 32 individuals were interviewed (28 carriers, 4 non-carriers). We interpreted five themes intersecting across six time points of the testing pathway: (1) individual differences regarding personal/family history of cancer, demographics and personal attitudes/approach; (2) healthcare professionals' support; (3) pathway access and integration; (4) nature of family/partner relationships; and (5) Jewish community factors. Testing was largely triggered by connecting information to a personal/family history of cancer. No participants reported decision regret, although there was huge variation in satisfaction. Suggestions were given around increasing UK Jewish community awareness, making information and support services personally relevant and proactive case management of carriers.CONCLUSIONS: There is a need to improve UK Jewish community BRCA awareness and to highlight personal relevance of testing for individuals without a personal/family history of cancer. Traditional testing criteria caused multiple issues regarding test access and experience. Carriers want information and support services tailored to their individual circumstances. </p

Cost-effectiveness of unselected multigene germline and somatic genetic testing for epithelial ovarian cancer

Background : Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)–based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. Methods: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. Results: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of$175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45$68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year’s testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. Conclusions: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone