Genetic testing is becoming rapidly more accessible to the general populous either through or outside healthcare systems. Few large-scale studies have been carried out to gauge public opinion in this growing area. Here, we undertook the largest cross-sectional study on genetic testing in the UK. The primary purpose of this study is to identify the differences in attitudes toward genetic testing across ethnic groups. A cohort of 6500 individuals from a diverse population completed a 72-item survey in a cross-sectional study. Responses between ethnic minority and white individuals in the UK were compared using a wilcoxon rank-sum and chi-square tests. The white cohort was approximately twice as likely to have taken a genetic test and 13% more had heard about genetic testing before the survey. The ethnic minority cohort appeared more apprehensive about the impact of genetic testing on employability. This study highlights that in the UK, significant differences in opinions regarding genetic testing exist between white individuals and ethnic minority individuals. There is an urgent need to develop more inclusive strategies to equally inform individuals from all backgrounds to avoid disparities in the utilisation of genetic testing.

As research uncovers the underpinnings of cancer biology, new targeted therapies have been developed. Many of these therapies are small molecules, such as kinase inhibitors, that target specific proteins; however, only 1% of the genome encodes for proteins and only a subset of these proteins has ‘druggable’ active binding sites. In recent decades, RNA therapeutics have gained popularity due to their ability to affect targets that small molecules cannot. Additionally, they can be manufactured more rapidly and cost-effectively than small molecules or recombinant proteins. RNA therapeutics can be synthesised chemically and altered quickly, which can enable a more personalised approach to cancer treatment. Even though a wide range of RNA therapeutics are being developed for various indications in the oncology setting, none has reached the clinic to date. One of the main reasons for this is attributed to the lack of safe and effective delivery systems for this type of therapeutic. This review focuses on current strategies to overcome these challenges and enable the clinical utility of these novel therapeutic agents in the cancer clinic.

Carboplatin remains integral for treatment of gynaecological malignancies and dosing is based on glomerular filtration rate (GFR). Measurement via radiotracer decay [nuclear medicine GFR (nmGFR)] is ideal. However, this may be unavailable. Therefore GFR is often estimated using formulae that have not been validated in patients with cancer and/or specifically for gynaecological malignancies, leading to debate over optimal estimation. Suboptimal GFR estimation may affect efficacy or toxicity. We surveyed several UK National Health Service Trusts to assess carboplatin dosing practise. We then explored single-centre accuracy, bias and precision of various formulae for GFR estimation, relative to nmGFR, before validating our findings in an external cohort. Across 18 Trusts, there was considerable heterogeneity in GFR estimation, including the formulae used [Cockcroft–Gault (CG) versus Wright], weight adjustment and area under the curve (AUC; 5 versus 6). We analysed 274 and 192 patients in two centres. Overall, CamGFR v2 (a novel formula for GFR estimation developed at Cambridge University Hospitals NHS Foundation Trust) excelled, showing the highest accuracy and precision. This translated into accuracy of hypothetical carboplatin dosing; nmGFR-derived carboplatin dose fell within 20% of the Cam GFR v2-derived dose in 86.5% and 87% of patients across the cohorts. Among the CG formula and its derivatives, using adjusted body weight in those with body mass index ≥25 kg/m² [CG-adjusted body weight (CG-AdBW)] was optimal. The Wright and unadjusted CG estimators performed most poorly. When compared with nmGFR assessment, accuracy, bias and precision varied widely between GFR estimators, with the newly developed Cam GFR v2 and CG-AdBW performing best. In general, weight (or body surface area)-adjusted formulae excelled, while the unadjusted CG and Wright formulae or the use of AUC6 (versus nmGFR AUC5) produced risk of significant overdose. Thus, individual centres should validate their GFR estimation methods. In the absence of validation, CG-AdBW or CamGFR v2 is likely to perform well while unadjusted CG/Wright formulae or AUC6 dosing should be avoided.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: The benefits and challenges of Electronic Health Record (EHR) use may be particularly significant in complex, high-risk specialties such as gynaecological oncology, yet few studies address the experiences of end-users. Objective: This study aimed to explore perspectives on EHR use in gynaecological oncology and to develop an informatics platform for ovarian cancer. Methods: A cross-sectional survey was conducted using a web-based questionnaire to capture UK professional experiences of EHR use. Free-text responses were analysed using content analysis; counts and proportions were calculated for quantitative data. An informatics platform was co-designed using human-centred design. Natural language processing was used to extract genomic results and operative details from free-text documentation. Results: Of 92 respondents, 84 (92.3%) access multiple electronic systems for clinical decision-making, with 28.6% (26/91) using ≥5 EHR systems. Around 17% (16/92) spend more than 50% of their clinical time looking for information in the EHR. Key challenges relate to fragmentation of the patient record across disparate systems meaning retrieval of pertinent information is often time-consuming. The main benefit of EHR use was perceived to be ease-of-access to patient information, yet 60.0% (54/90) of respondents do not have access to individual patient summaries. Our co-designed ovarian cancer informatics platform brings together patient data from different electronic systems and displays it in a single location to support clinical decision making. Conclusions: EHR systems are not currently optimised to support decision-making in gynae-oncology. Co-designed clinical decision support tools could address challenges with data fragmentation and information retrieval towards improvements in the quality and safety of cancer care.

Purpose: High grade serous carcinoma (HGSC) is the commonest type of ovarian cancer. Nearly all HGSC cases are diagnosed at late stage and it is not clear whether early stage HGSC has unique characteristics compared to late stage tumours. Experimental Design: We analysed samples from 45 patients with FIGO stage I - IIA HGSC - 40 from the pathology archives of three large UK cancer centres and 5 from the BriTROC-1 study. We performed shallow whole genome sequencing (sWGS) and targeted next generation sequencing to investigate somatic mutations and copy number alterations. We compared results to 51 stage IIIC/IV HGSC patients from the BriTROC-1 study. Results: There was no difference in median age between the early stage (median 61.3 years, range 40-84) and late stage (median 62.3 years, range 34-76) patients at diagnosis. TP53 mutations were near-universal (92% early stage, 100% late stage samples) and there were no significant differences in the rates of other somatic mutations, including BRCA1 and BRCA2 , or focal copy number alterations between early- and late-stage cohorts. There were also no unique amplifications or deletions in either cohort. However, median ploidy was greater in late stage (median 3.1) than early stage (median 2.0) samples. In addition, there were higher numbers of breakpoints per 10MB and per chromosome arm and higher absolute copy number in late stage than early stage cohorts; early stage samples had longer segment length. Overall copy number signature exposures were significantly different between early and late stage samples with greater signature 3 exposure in early stage and greater signature 4 in late stage. Both simplex plot and unsupervised hierarchical clustering suggested that a subset of late stage samples retain early stage appearances with high signature 3 and co-clustering with the early stage samples Conclusions: These data suggest that there are no unique mutations or focal copy number alterations in early stage HGSC. However, whole genome duplication is significantly more common in late-stage disease, suggesting evolution during disease progression. However, a subset of late stage HGSC retains early-stage features, which are associated with improved overall survival.

Mainstreaming patients with ovarian, endometrial, and colorectal cancer in the context of genetic testing at cancer diagnosis involves pre-test counseling, consent, and return of results by the clinical cancer team. This process uses significant clinician time and resources. Alternative implementation strategies might be more cost-efficient and better utilize limited cancer health professional and genetics workforce resources, but their efficacy is less well understood. To determine if direct-to-patient genetic testing for ovarian, endometrial, and colorectal cancer has equivalent uptake of genetic testing compared with mainstreaming. Patients at ovarian, endometrial, or colorectal cancer diagnosis have equivalent uptake for genetic testing through direct-to-patient compared with mainstreaming. A multicenter randomized controlled trial evaluating a digitally enabled direct-to-patient (saliva-based, at home) genetic testing approach (intervention arm) compared with mainstreaming genetic testing (control arm). After study consent and randomization, patients in the direct-to-patient arm are offered access to an app-based decision aid, consent to genetic testing via the app, and access to a helpline for additional support and counseling if needed. Control arm participants are offered routine mainstreaming genetic testing in the clinic. We include a qualitative sub-study of 1:1 interviews to understand the attitudes, experiences, and impact on emotional well-being of patients undergoing genetic testing. Inclusion criteria include diagnosis of ovarian, endometrial, or colorectal cancer fulfilling the National Health Service clinical genetic testing criteria. Exclusion criteria include prior genetic testing for or a known familial pathogenic variant in ovarian, endometrial, or colorectal cancer susceptibility genes. Absolute difference in uptake of genetic testing between arms in the intention-to-treat population, with equivalence determined using a 10% margin based on a 2-sided 95% confidence interval. Target n = 626 to 832 patients. We will test equivalence if ≥626 patients are recruited in the intention-to-treat population. Recruitment by December 2026 and publication of results in 2028. ISRCTN:57402067 (July 26, 2023). (https://doi.org/10.1186/ISRCTN57402067).