Background. Cancer is a leading cause of mortality in the United Kingdom (UK). Survival is improved when patients receive curative treatment ('treatment receipt'), with further improvements when such treatment is initiated early (shorter 'time-to-treatment') and implementation of treatment is adherent with the treatment plan ('treatment adherence'). However, various factors can influence each of these stages, affecting whether patients receive treatment, how soon they start treatment and whether they adhere to treatment. Although such barriers and facilitators are widely discussed in the literature, the evidence base remains fragmented, with no reviews synthesising what is currently known about the factors that hinder treatment receipt, timeliness and adherence. Aims. The aims of this review are to: 1) collate, extract and synthesise existing literature from the UK and the Republic of Ireland that investigates the barriers and facilitators to cancer treatment receipt, time-to-treatment and treatment adherence, and 2) identify knowledge gaps for future research. Methods. To address these aims, we are conducting a scoping review, using the six-stage framework described by Arksey and O'Malley, which includes (1) defining the research question, (2) identifying relevant studies, (3) selecting studies, (4) charting the data, (5) synthesizing and reporting results, and (6) consulting with stakeholders. The first two stages have been completed, the third stage is in progress and the last three stages have not yet been started. The research question was formulated using the PCC mnemonic: 'Population (adults with cancer, or carers or healthcare professionals supporting adults with cancer), Concept (barriers and/or facilitators to treatment receipt, time-to-treatment or treatment adherence), and Context (UK and Republic of Ireland).' A comprehensive search strategy was developed by incorporating key words and Medical Subject Headings (MeSH) to capture qualitative studies, mixed-methods studies and quantitative surveys exploring psychological, social, practical or access-related barriers and facilitators to curative cancer treatment. The search strategy was applied to Web of Science, Embase, Medline, CINAHL, PsychINFO and Google Scholar. Articles published ≥2011, available in English, involving adults (≥18 years) with cancer, carers or healthcare professionals supporting adults with cancer in the UK or Republic of Ireland, which examined barriers and/or facilitators to curative treatment, time-to-treatment, or treatment adherence were deemed eligible. We excluded studies involving individuals 3c18 years, studies that collected data prior to 2011, studies focussing solely on non-curative treatments (e.g. palliative or end of life care), grey literature and studies outside of the UK or Republic of Ireland (unless part of a multi-country study including these settings, where UK or Republic of Ireland-specific data could be extracted). In total, 4,239 unique articles have been identified, 247 passed title and abstract review and 100 passed full text review. Data from included studies is now being extracted using a standardised data extraction form developed by the authors to facilitate a descriptive and narrative synthesis. All results will be reported in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR) and will be disseminated through a written manuscript detailing the findings. The methods used throughout the scoping review and the interpretation of findings will be reviewed by specialist oncologists, patients and members of the public.

Open Science (OS) promises to democratise knowledge and reduce epistemic inequalities. However, a critical analysis reveals the potential of OS to amplify structural vulnerabilities, especially for people and communities already at the margins. With a particular focus on health data, this interdisciplinary essay examines how OS infrastructures perpetuate epistemic harms through the dominance of Eurocentric knowledge norms, legal regimes and corporate capture. Amidst the rapidly evolving health and data landscape, realising the social justice potential of OS, especially in healthcare, demands moving beyond techno-optimism to approaches that centre plural epistemologies, relational accountability and community empowerment.

ABSTRACT Background Lynch syndrome (LS) is a cancer susceptibility syndrome caused by germline pathogenic variants in DNA mismatch repair (MMR) genes. Due to increased risk of colorectal cancer (CRC), enhanced colonoscopic surveillance is recommended for heterozygote MMR-carriers. Objective Using a registry of English LS patients linked to digital National Health Service records, we aimed to assess adherence of MMR-carriers to national surveillance guidelines, and to determine the impact of surveillance on CRC incidence and mortality. Design We described the frequency of colonoscopies in 4,732 MMR-carriers and used logistic regression to determine predictors of surveillance adherence. For MMR-carriers with a record of surveillance and those without, we: estimated age-specific annual CRC incidence rates (AS-AIRs) and cumulative lifetime risks, assessed for stage-shift by comparing CRC stage distributions and stage-specific AS-AIRs, and estimated risks of death from CRC and any cause using Kaplan-Meier methods and Cox Proportional Hazards regression. Results Surveillance at a mean interval of ≤ 3 years (n=3028) was associated with a decrease in CRC-specific and all-cause mortality, without an associated change in total CRC incidence, even after multivariate adjustment. No strong evidence of stage-shift was observed. Colonoscopic surveillance at a mean interval of ≤ 2 years (n=1569) was associated with an increase in total CRC incidence. Incidence of early-stage cancers was also higher, with no corresponding decrease in late-stage cancers, which may reflect the short follow-up period or the impact of overdiagnosis. Conclusion The observed reduction in all-cause mortality amongst regularly-surveilled MMR-carriers may indicate an impact of surveillance on CRC-specific mortality, though in the context of a non-randomised study likely reflects the influence of selection bias. KEY MESSAGES OF ARTICLE What is already known on this topic Regular surveillance colonoscopy is recommended in Lynch syndrome, though evidence to support this remains mixed. We searched PubMed for articles published from inception to 01/05/2024 using the terms “Lynch syndrome”, “HNPCC”, “colonoscopy”, “sigmoidoscopy”, “surveillance”, and “screening”. We found one controlled trial and several small analytical studies dating from the early 2000s which compared surveilled and non-surveilled populations and found surveillance to be associated with reduced colorectal cancer (CRC) incidence and improved survival. More recent longitudinal observational studies, most without comparator groups, found a high incidence of CRC in LS populations despite being resident in countries where surveillance was recommended. A small number of studies directly assessed time since last colonoscopy against CRC incidence and stage with mixed findings. Finally, cross-sectional comparisons between countries of CRC incidence rates and surveillance interval recommendations found no relationship between the two 1,2 . What this study adds Here, we conduct an observational cohort study on a large national cohort of MMR germline pathogenic variant (GPV) carriers (MMR-carriers) in England (n=4,732), comparing CRC incidence and mortality in individuals with a record of regular surveillance to those without. Through linkage of the English National Lynch Syndrome Registry to Hospital Episodes Statistics data, we are uniquely able to study a comprehensive national population of MMR-carriers and identify the dates on which colonoscopies were undertaken over time, allowing assessment of adherence to national surveillance guidelines and the impact this has on CRC outcomes. Notably, receipt of regular colonoscopy was strongly associated with deprivation as well as ethnicity. The results show that regular surveillance at an average interval of 3 years (or less) is not associated with a reduction in CRC incidence when compared to less frequent surveillance, but an apparent decrease in both CRC-specific and overall mortality is observed, even after adjustment for confounding variables. Conversely, regular surveillance at an average interval of 2 years (or less) is associated with an increase in CRC incidence when compared to less frequent surveillance, which may suggest increased diagnosis of early-stage cancers or, due to the absence of a reduction in late-stage cancers, overdiagnosis. The observed impact of surveillance on overall mortality may demonstrate the impact of surveillance on CRC-specific mortality, or, in the context of an observational (non-randomised) study, indicate that the results are subject to selection bias. How this study might affect research, practice, or policy Evidence for the benefit of surveillance colonoscopy remains mixed. Whilst polypectomy would be anticipated to prevent CRC development (thus reducing CRC incidence), several studies have observed increased frequency of CRCs in MMR-carriers undergoing frequent surveillance colonoscopy, which may reflect overdiagnosis. The selection bias inherent to observational studies of surveillance renders mortality outcomes challenging to interpret. Randomised controlled trials of colonoscopic surveillance in MMR-carriers are required for effectiveness of this intervention to be accurately assessed. Given ethical and feasibility challenges, randomised controlled trials might be complemented by quasi-experimental designs using advanced observational methods for assessing effectiveness.

AIM:There is no consensus for the use of adjuvant chemotherapy (ACT) after radical resection in rectal cancer. We use real-world data from the Netherlands (NL), England and Scotland, from patients who underwent surgery without neoadjuvant chemotherapy, to explore the potential benefit of ACT. MATERIALS AND METHODS:Routine administrative healthcare data from the NL (2012-2017), England (2014-2019) and Scotland (2013-2017) were used to identify patients with a clinical or pathological T3, T4, or N+ rectal cancer; managed with radical resection ± neoadjuvant (chemo)radiotherapy. Data on patient, tumour, treatment demographics and survival were collected. Kaplan-Meier curves and Cox regression models were used to understand the association between ACT and 5-year survival. Models were estimated for the total population and different pre-defined subgroups within each cohort, unadjusted and adjusted for relevant confounding factors. RESULTS:33,211 patients were included, 12,649, 18,729 and 1833 patients from NL, English and Scottish cohorts, respectively. ACT use differed with administration rates of 3.6%, 34.4% and 33.1%, respectively. The use of neo-adjuvant (chemo)radiotherapy was higher in NL (75·7%, 36.2% and 42.3%, respectively). The Hazard Ratio for death at 5 years was in favour of ACT in all three cohorts, reaching statistical significance in the English and Scottish cohorts (adjusted HR 0.66, 95% CI 0.61-0.71) and (adjusted HR 0.50, 95% CI 0.37-0.68), respectively. CONCLUSIONS:Whilst this survival benefit must be interpreted with caution due to the limitations of real-world data, in the absence of high-level evidence, it offers further weight to contemporary rectal cancer literature that multimodality treatment including systemic therapy offers an OS in rectal cancer.

Objectives To investigate the association between bilateral salpingo-oophorectomy (BSO) and long-term health outcomes in women with a personal history of breast cancer.Methods and analysis We used data on women diagnosed with invasive breast cancer between 1995 and 2019 from the National Cancer Registration Dataset (NCRD) in England. The data were linked to the Hospital Episode Statistics-Admitted Patient Care dataset to identify BSO delivery. Long-term health outcomes were selected from both datasets. Multivariable Cox regression was used to examine the associations, with BSO modelled as a time-dependent covariate. The associations were investigated separately by age at BSO.Results We identified 568 883 women, 23 401 of whom had BSO after the breast cancer diagnosis. There was an increased risk of total cardiovascular diseases with an HR of 1.10 (95% CI 1.04 to 1.16) in women who had BSO<55 years and 1.07 (95% CI 1.01 to 1.13) for women who had BSO≥55 years. There was an increased risk of ischaemic heart diseases, but there was no association with cerebrovascular diseases. BSO at any age was associated with an increased risk of depression (HR 1.20, 95% CI 1.12 to 1.28) and increased risk of second non-breast cancer in older women (HR 1.21, 95%CI 1.08 to 1.35). BSO in older women was associated with reduced risk of all-cause mortality (HR 0.92, 95% CI 0.87 to 096), but not in women who had BSO<55 years.Conclusion In women with a personal history of breast cancer, BSO before and after the age of 55 years is associated with an increased risk of long-term outcomes. BSO after 55 years is associated with reduced all-cause mortality. Family history or genetic predisposition may confound these associations.

OBJECTIVE:To describe the distribution of disease stages, receipt of major surgery, 1-year net survival (NS) and 1-year conditional NS in relation to age and frailty in adults aged ≥50 diagnosed with colon cancer in England. METHODS:We obtained data on adults aged 50-99 diagnosed with colon cancer between 2014 and 2019, followed up through December 2021, from the national population-based COloRECTal cancer Repository. Frailty was assessed using the Secondary Care Administrative Records Frailty (SCARF) index categorised into fit, mild, moderate and severe frailty. Data on major resection were obtained through linkage with Hospital Episode Statistics dataset. Major resection rates were calculated in adults with stage I-III cancer. Descriptive statistics were used as appropriate. One-year NS from cancer diagnosis and 1-year conditional NS were estimated using the Pohar-Perme estimator. RESULTS:Out of 130 360 individuals (48% females-50% over 75), 48.9% were fit, ranging from 69% in the 50-64 age group to 31% in the 85-99 age group. Over 80% of adults with stage I-III cancer underwent a major resection. This percentage was 58% amongst fit adults aged over 85. One-year NS decreased as age increased across all frailty levels. Differences in NS between the 50-64 age group and the 85-99 age group were reduced in adults who survived beyond 1 year from diagnosis except for severely frail adults. CONCLUSION:This population-based study shows that a non-negligible proportion of older adults diagnosed with colon cancer and deemed 'fit' through the SCARF did not receive surgery that may impact their survival.

ObjectiveStudies in the USA examining the relationship between ethnicity and colorectal cancer (CRC) identified significant variation. This study sought to examine the relationship between ethnic group, route to diagnosis, early-onset CRC and stage at diagnosis in the English National Health Service.MethodsData from COloRECTal cancer data Repository for all individuals diagnosed with CRC (International Classification of Diseases version 10, C18–C20) between 2012 and 2017. A descriptive analysis of the characteristics of the study population was performed. Multivariable logistic regression models were used to assess the association between ethnicity, route to diagnosis, stage at diagnosis and early-onset CRC.ResultsEarly-onset CRC was least common in those in the white ethnic group (5.5% diagnosed <50, vs 17.9% in the Asian, 15.5% in the black and 21.8% in the mixed and multiple ethnic groups, p<0.01). Diagnosis following a 2-week wait referral was significantly less common among individuals from the Asian, black, other and unknown ethnic groups than the white ethnic group (Asian OR 0.84, 95% CI 0.79 to 0.91, black OR 0.86, 95% CI 0.79 to 0.93, other OR 0.81, 95% CI 0.73 to 0.90 and unknown OR 0.70, 95% CI 0.66 to 0.73). The Asian ethnic group had significantly lower odds of emergency diagnosis than the white ethnic group (OR 0.90, 95% CI 0.83 to 0.97). Following adjustment, individuals from the Asian ethnic group were significantly less likely, than their white counterparts, to be diagnosed at stage IV (OR 0.82, 95% CI 0.76 to 0.88).ConclusionThis study identified different demographic profiles of those diagnosed with CRC between broad ethnic groups, highlighting the need to consider access to diagnostic CRC services in the context of ethnicity.

BACKGROUND:Carriers of BRCA1 and BRCA2 pathogenic variants are at elevated risk of developing breast and ovarian cancers. To mitigate ovarian cancer risk, bilateral salpingo-oophorectomy (BSO) is commonly recommended for unaffected carriers and those with personal breast cancer history. Assessing BSO's long-term health outcomes in carriers with previous breast cancer history is essential. This study aims to examine the association between BSO and long-term health outcomes in individuals carrying pathogenic variants in BRCA1 and BRCA2 and with personal history of breast cancer. METHODS:Data from the National Cancer Registration Dataset (NCRD) were linked with data from genetic testing laboratories to identify carriers of BRCA1 and BRCA2 pathogenic variants affected by breast cancer using pseudonymised patient identifiers. Further linkage to the Hospital Episode Statistics-Admitted Patient Care (HES-APC) dataset identified patients who had undergone BSO. Women aged 20-75 years, with a diagnosis of breast cancer as their first primary malignancy in 1995-2019 were eligible. Long-term health outcomes were identified from HES-APC and NCRD. Missing data were imputed using multivariate imputations by chained equations. Multivariable Cox regression was used to examine the associations with mortality (all-cause mortality, breast cancer-specific mortality, and non-breast cancer-specific mortality), second non-breast cancer, cardiovascular diseases, ischaemic heart disease, cerebrovascular diseases, contralateral breast cancer, and depression. Analyses were adjusted for age at diagnosis, diagnosis year, ethnicity, deprivation index, tumour characteristics, Charlson comorbidity index, cancer treatment, and second cancer diagnosis before the start of follow-up. FINDINGS:We included 1674 BRCA1, 1740 BRCA2, and nine BRCA1 and BRCA2 carriers who were diagnosed with breast cancer between 1995 and 2019, with median follow-up time of 5·5 years (IQR 3·4-8·2). The study population (n=3423) consisted of 3002 (88·7%) White, 170 (5·0%) Asian, 59 (1·7%) Black, 26 (0·8%) mixed, and 74 (2·2%) other ethnic groups, and 92 (2·7%) had missing ethnicity. The uptake of BSO was significantly lower among Black women (odds ratio [OR] vs White women 0·48, 95% CI 0·34-0·67), and Asian women (0·47, 0·27-0·82). BSO uptake was higher in women living in the least socioeconomically deprived areas (OR vs most deprived 1·38, 95% CI [1·10-1·72]). BSO was associated with a reduced risk of all-cause mortality for both BRCA1 and BRCA2 pathogenic variant carriers (HR 0·52, 95% CI 0·41-0·64) and reduced breast cancer-specific mortality (BRCA1: HR 0·62, 95% CI 0·42-0·92 and BRCA2: 0·48, 0·34-0·68). It was also associated with a reduced risk of second non-breast cancer in the combined BRCA1 and BRCA2 sample (HR 0·59, 95% CI 0·37-0·94). There BSO was not associated with increased risk of cardiovascular diseases (HR 0·73, 95% CI 0·53-1·01), ischaemic heart disease (1·04, 0·48-2·26), cerebrovascular disease (0·32, 0·11-0·90), non-breast cancer specific mortality (0·72, 0·45-1·16), contralateral breast cancer (1·18, 0·64-2·16), or depression (0·94, 0·62-1·42). INTERPRETATION:The evidence supports offering BSO to BRCA1 and BRCA2 pathogenic variant carrriers with a personal history of breast cancer, as they appear to benefit from having the procedure, without evidence of an increased risk of adverse long-term health outcomes. FUNDING:Cancer Research UK.

PURPOSE Second primary cancer (SPC) risks after breast cancer (BC) in BRCA1/BRCA2 pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records. METHODS We followed 25,811 females and 480 males diagnosed with BC and tested for germline BRCA1/BRCA2 PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks. RESULTS There were 1,840 BRCA1 and 1,750 BRCA2 female PV carriers. Compared with population incidences, BRCA1 carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. BRCA2 carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without BRCA1/BRCA2 PVs on testing, BRCA1 carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. BRCA2 carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% ( BRCA1 carriers), 12%/3.0%/6.2% ( BRCA2 carriers), and 3.6%/0.4%/4.9% (noncarriers). Male BRCA2 carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers. CONCLUSION Survivors of BC carrying BRCA1 and BRCA2 PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.

Abstract Background Stage IV rectal cancer carries a 10% 5-year survival rate (Jemal et al., 2005). Curative-intent management requires treatment of both the primary and metastatic disease. This study aimed to identify patterns in stage IV rectal cancer treatment pathway at population level across the UK, and to identify predictors of treatment pathway completion. Method Patient demographics and treatment data were extracted from the UK Colorectal Cancer Intelligence Hub’s CORECT-R repository, national chemotherapy (SACT), radiotherapy datasets (RTDS), and Hospital Episode Statistics (HES) data. Treatment pathway completion was defined as receipt of intervention to the primary tumour, in addition to metastasis-directed therapy, or the combination alongside chemotherapy. Multivariable logistic regression analysis was performed to identify independent predictors of treatment completion. Results A total of 15,727 patients with stage IV rectal cancer diagnosed between 2010-19 were identified. There was significant variation in proportion of patients with complete treatment between MDTs. Multivariable analyses showed that lack of on-site HPB surgery capability was the only predictor of failure to complete treatment (OR 1.22, 95%CI:1.07-1.38, p<0.01). Conclusion Across the UK, there is variation in Stage IV rectal cancer patients completing treatment for both their primary and metastatic disease. Further work is needed to determine whether differences in treatment pathways stem from variation in access to specialist services between cancer alliances or whether they are due to differences in MDT decision making.

Background For female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS.Methods A retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset. For all EC diagnosed in 2019, the proportion tested, median time to test, yield of abnormal results and factors influencing testing pathway initiation were examined.Results There was an immunohistochemistry (IHC) or microsatellite instability (MSI) test recorded for 17.8% (1408/7928) of patients diagnosed with EC in 2019. Proportions tested varied by Cancer Alliance and age. There was an MLH1 promoter hypermethylation test recorded for 43.1% (149/346) of patients with MLH1 protein IHC loss or MSI. Of patients with EC eligible from tumour-testing, 25% (26/104) had a germline MMR test recorded. Median time from cancer diagnosis to germline MMR test was 315 days (IQR 222-486).Conclusion This analysis highlights the regional variation in recorded testing, patient attrition, delays and missed opportunities to diagnose LS, providing an informative baseline for measuring the impact of the national guidance from the National Institute for Health and Care Excellence on universal reflex LS testing in EC, implemented in 2020.

Background:Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established. Methods:For comprehensive ascertainment of retrospectively identified MMR pathogenic variant (PV) carriers (diagnosed prior to January 1, 2023), information was retrieved from all clinical genetics services across England, then restructured, amalgamated, and validated via a team of trained experts in NDRS. An online submission portal was established for prospective ascertainment from January 1, 2023. The resulting data, stored in a secure database in NDRS, were used to investigate the demographic and genetic characteristics of the cohort, censored at July 25, 2023. Cancer outcomes were investigated via linkage to the National Cancer Registration Dataset (NCRD). Findings:A total of 11,722 retrospective and 570 prospective data submissions were received, resulting in a comprehensive English National Lynch Syndrome Registry (ENLSR) comprising 9030 unique individuals. The most frequently identified pathogenic MMR genes were MSH2 and MLH1 at 37.2% (n = 3362) and 29.1% (n = 2624), respectively. 35.9% (n = 3239) of the ENLSR cohort received their LS diagnosis before their first cancer diagnosis (presumptive predictive germline test). Of these, 6.3% (n = 204) developed colorectal cancer, at a median age of initial diagnosis of 51 (IQR 40-62), compared to 73 years (IQR 64-80) in the general population (p < 0.0001). Interpretation:The ENLSR represents the first comprehensive national registry of PV carriers in England and one of the largest cohorts of MMR PV carriers worldwide. The establishment of a secure, centralised infrastructure and mechanism for routine registration of newly identified carriers ensures sustainability of the data resource. Funding:This work was funded by the Wellcome Trust, Cancer Research UK and Bowel Cancer UK. The funder of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

BACKGROUND:Post-endoscopy upper gastrointestinal cancer (PEUGIC) is an important key performance indicator for endoscopy quality. We examined variation in PEUGIC rates among endoscopy providers in England and explored associated factors. METHODS:The was a population-based, retrospective, case-control study, examining data from National Cancer Registration and Analysis Service and Hospital Episode Statistics databases for esophageal and gastric cancers diagnosed between 2009 and 2018 in England. PEUGIC were cancers diagnosed 6 to 36 months after an endoscopy that did not diagnose cancer. Associated factors were identified using multivariable logistic regression analyses. RESULTS:The national PEUGIC rate was 8.5%, varying from 5% to 13% among endoscopy providers. Factors associated with PEUGIC included: female sex (odds ratio [OR] 1.29 [95%CI 1.23-1.36]); younger age (age >80 years, OR 0.52 [0.48-0.56], compared with ≤60 years); increasing comorbidity (Charlson score >4, OR 5.06 [4.45-5.76]); history of esophageal ulcer (OR 3.30 [3.11-3.50]), Barrett's esophagus (OR 3.21 [3.02-3.42]), esophageal stricture (OR 1.28 [1.20-1.37]), or gastric ulcer (OR 1.55 [1.44-1.66]); squamous cell carcinoma (OR 1.50 [1.39-1.61]); and UK national endoscopy accreditation status - providers requiring improvement (OR 1.10 [1.01-1.20]), providers never assessed (OR 1.24 [1.04-1.47]). CONCLUSION:PEUGIC rates varied threefold among endoscopy providers, suggesting unwarranted differences in endoscopy quality. PEUGIC was associated with endoscopy findings known to be associated with upper gastrointestinal cancer and a lack of national endoscopy provider accreditation. PEUGIC variations suggest an opportunity to raise performance standards to detect upper gastrointestinal cancers earlier and improve outcomes.

BACKGROUND:The uptake of minimally invasive surgery (MIS) for patients with colorectal cancer has progressed at differing rates, both across countries, and within countries. This study aimed to investigate uptake for a regional colorectal cancer improvement programme in England. METHOD:We calculated the proportion of patients receiving elective laparoscopic and robot-assisted surgery amongst those diagnosed with colorectal cancer over 3 time periods (2007-2011, 2012-2016 and 2017-2021) in hospitals participating in the Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR BCIP). These were benchmarked against national rates. Regression analysis and funnel plots were used to develop a data driven approach for analysing trends in the use of MIS at hospitals in the programme. RESULTS:In England, resections performed by MIS increased from 34.9% to 72.9% for colon cancer and from 28.8% to 72.5% for rectal cancer. Robot-assisted surgery increased from 0.1% to 2.7% for colon cancer and from 0.2% to 7.9% for rectal cancer. Wide variation in the uptake of MIS was observed at a hospital level. Detailed analysis of the YCR BCIP region identified a decreasing number of surgical departments, since the start of the programme, as potential outliers for MIS when compared to the English national average. CONCLUSION:Wide variation in use of MIS for colorectal cancer exists within the English National Health Service and a data-driven approach can help identify outlying hospitals. Addressing some of the challenges behind the uptake of MIS, such as ensuring adequate provision of surgical training and equipment, could help increase its use.

Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects, is enhanced by understanding how the trial population may differ from the populations it aims to represent. We compared baseline characteristics and mortality of RECOVERY participants recruited in England (n = 38,510) with a reference population hospitalised with COVID-19 in England (n = 346,271) from March 2020 to November 2021. We used linked hospitalisation and mortality data for both cohorts to extract demographics, comorbidity/frailty scores, and crude and age- and sex-adjusted 28-day all-cause mortality. Demographics of RECOVERY participants were broadly similar to the reference population, but RECOVERY participants were younger (mean age [standard deviation]: RECOVERY 62.6 [15.3] vs reference 65.7 [18.5] years) and less frequently female (37

Summary: Background: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets. Methods: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019. We estimated standardized incidence ratios (SIRs) for combined and site-specific SPCs using incidences for England, overall and by age at BC and socioeconomic status. We estimated incidences and Kaplan–Meier cumulative risks stratified by age at BC, and assessed risk variation by socio-demographic, tumour, and treatment characteristics using Cox regression. Findings: Both genders were at elevated contralateral breast (SIR: 2.02 (95% CI: 1.99–2.06) females; 55.4 (35.5–82.4) males) and non-breast (1.10 (1.09–1.11) females, 1.10 (1.00–1.20) males) SPC risks. Non-breast SPC risks were higher for females younger at BC diagnosis (SIR: 1.34 (1.31–1.38) <50 y, 1.07 (1.06–1.09) ≥50 y) and more socioeconomically deprived (SIR: 1.00 (0.98–1.02) least deprived quintile, 1.34 (1.30–1.37) most). Interpretation: Enhanced SPC surveillance may benefit BC survivors, although specific recommendations require more detailed multifactorial risk and cost-benefit analyses. The associations between deprivation and SPC risks could provide clinical management insights. Funding: CRUK Catalyst Award CanGene-CanVar (C61296/A27223). Cancer Research UK grant: PPRPGM-Nov 20∖100,002. This work was supported by core funding from the NIHR Cambridge Biomedical Research Centre (NIHR203312)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Spain is one of the most heavily affected countries by the Covid-19 pandemic. In this study, we estimated the regional inequalities in excess deaths and premature mortality in Spain. Between January 2020 and June 2021, an estimated 89,200 (men: 48,000; women: 41,200) excess deaths occurred in the 17 Spanish regions with a substantial variability (highest in Madrid: 22,000, lowest in Canary Islands: -210). Highest reductions in life expectancy at birth (e_0) in 2020 were observed in Madrid (men: -3.48 years, women: -2.15), Castile La Mancha (men: -2.67, women: -2.30), and Castile and Leon (men: -2.00, women: -1.32). In the first six months of 2021, the highest reduction in e_0 was observed in Valencian Community (men: -2.04, women: -1.63), Madrid (men: -2.37), and Andalusia (men: -1.75; women: -1.43). In some Spanish regions, life expectancy at age 65 during the Covid-19 pandemic in 2020 was comparable to that observed as far back as 20 years ago.

Background National and international amalgamation of genomic data offers opportunity for research and audit, including analyses enabling improved classification of variants of uncertain significance. Review of individual-level data from National Health Service (NHS) testing of cancer susceptibility genes (2002-2023) submitted to the National Disease Registration Service revealed heterogeneity across participating laboratories regarding (1) the structure, quality and completeness of submitted data, and (2) the ease with which that data could be assembled locally for submission.Methods In May 2023, we undertook a closed online survey of 51 clinical scientists who provided consensus responses representing all 17 of 17 NHS molecular genetic laboratories in England and Wales which undertake NHS diagnostic analyses of cancer susceptibility genes. The survey included 18 questions relating to 'next-generation sequencing workflow' (11), 'variant classification' (3) and 'phenotypical context' (4).Results Widely differing processes were reported for transfer of variant data into their local LIMS (Laboratory Information Management System), for the formatting in which the variants are stored in the LIMS and which classes of variants are retained in the local LIMS. Differing local provisions and workflow for variant classifications were also reported, including the resources provided and the mechanisms by which classifications are stored.Conclusion The survey responses illustrate heterogeneous laboratory workflow for preparation of genomic variant data from local LIMS for centralised submission. Workflow is often labour-intensive and inefficient, involving multiple manual steps which introduce opportunities for error. These survey findings and adoption of the concomitant recommendations may support improvement in laboratory dataflows, better facilitating submission of data for central amalgamation.