Effects on Cancer Prevention from the COVID-19 Pandemic.

The COVID-19 pandemic led to disruption of health services around the world, including cancer services. We carried out a narrative review of the effect of the pandemic on cancer prevention services, including screening. Services were severely affected in the early months of the pandemic, and in some areas are still recovering. Large numbers of additional cancers or additional late-stage cancers have been predicted to arise over the coming years as a result of this disruption. To minimize the effects on cancer outcomes, it is necessary to return as quickly as possible to prepandemic levels of screening and prevention activity or indeed to exceed these levels. The recovery of services should address health inequalities.

The cost-effectiveness of risk-stratified breast cancer screening in the UK.

BACKGROUND: There has been growing interest in the UK and internationally of risk-stratified breast screening whereby individualised risk assessment may inform screening frequency, starting age, screening instrument used, or even decisions not to screen. This study evaluates the cost-effectiveness of eight proposals for risk-stratified screening regimens compared to both the current UK screening programme and no national screening. METHODS: A person-level microsimulation model was developed to estimate health-related quality of life, cancer survival and NHS costs over the lifetime of the female population eligible for screening in the UK. RESULTS: Compared with both the current screening programme and no screening, risk-stratified regimens generated additional costs and QALYs, and had a larger net health benefit. The likelihood of the current screening programme being the optimal scenario was less than 1%. No screening amongst the lowest risk group, and triannual, biennial and annual screening amongst the three higher risk groups was the optimal screening strategy from those evaluated. CONCLUSIONS: We found that risk-stratified breast cancer screening has the potential to be beneficial for women at the population level, but the net health benefit will depend on the particular risk-based strategy.

Quantifying the effects of risk-stratified breast cancer screening when delivered in real time as routine practice versus usual screening: the BC-Predict non-randomised controlled study (NCT04359420).

BACKGROUND: Risk stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) could provide a better balance of benefits and harms. We developed BC-Predict, to offer women when invited to the NHSBSP, which collects standard risk factor information; mammographic density; and in a sub-sample, a Polygenic Risk Score (PRS). METHODS: Risk prediction was estimated primarily from self-reported questionnaires and mammographic density using the Tyrer-Cuzick risk model. Women eligible for NHSBSP were recruited. BC-Predict produced risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5-<8% 10-year) to have appointments to discuss prevention and additional screening. RESULTS: Overall uptake of BC-Predict in screening attendees was 16.9% with 2472 consenting to the study; 76.8% of those received risk feedback within the 8-week timeframe. Recruitment was 63.2% with an onsite recruiter and paper questionnaire compared to <10% with BC-Predict only (P < 0.0001). Risk appointment attendance was highest for those at high risk (40.6%); 77.5% of those opted for preventive medication. DISCUSSION: We have shown that a real-time offer of breast cancer risk information (including both mammographic density and PRS) is feasible and can be delivered in reasonable time, although uptake requires personal contact. Preventive medication uptake in women newly identified at high risk is high and could improve the cost-effectiveness of risk stratification. TRIAL REGISTRATION: Retrospectively registered with clinicaltrials.gov (NCT04359420).

Impact of radiographer immediate reporting of X-rays of the chest from general practice on the lung cancer pathway (radioX): a randomised controlled trial.

The National Optimal Lung Cancer Pathway recommends rapid progression from abnormal chest X-rays (CXRs) to CT. The impact of the more rapid reporting on the whole pathway is unknown. The aim of this study was to determine the impact of immediate reporting of CXRs requested by primary care by radiographers on the time to diagnosis of lung cancer. METHOD: People referred for CXR from primary care to a single acute district general hospital in London attended sessions that were prerandomised to either immediate radiographer (IR) reporting or standard radiographer (SR) reporting within 24 hours. CXRs were subsequently reported by radiologists blind to the radiographer reports to test the reliability of the radiographer report. Radiographer and local radiologist discordant cases were reviewed by thoracic radiologists, blinded to reporter. RESULTS: 8682 CXRs were performed between 21 June 2017 and 4 August 2018, 4096 (47.2%) for IR and 4586 (52.8%) for SR. Lung cancer was diagnosed in 49, with 27 (55.1%) for IR. The median time from CXR to diagnosis of lung cancer for IR was 32 days (IQR 19, 70) compared with 63 days (IQR 29, 78) for SR (p=0.03).8258 CXRs (95.1%) were reported by both radiographers and local radiologists. In the 1361 (16.5%) with discordance, the reviewing thoracic radiologists were equally likely to agree with local radiologist and radiographer reports. CONCLUSIONS: Immediate reporting of CXRs from primary care reduces time to diagnosis of lung cancer by half, likely due to rapid progress to CT. Radiographer reports are comparable to local radiologist reports for accuracy. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN21818068. Registered on 20 June 2017.

Barriers to colonoscopy in UK colorectal cancer screening programmes: Qualitative interviews with ethnic minority groups.

OBJECTIVE: People from ethnic minority backgrounds are less likely to attend colonoscopy, following faecal immunochemical test screening, and are more likely to be diagnosed with colorectal cancer at an advanced stage as a result. The aim of this research was to explore the barriers and facilitators to attending colonoscopy, perceived by ethnic minority groups living in the United Kingdom. METHODS: Semi-structured online and telephone interviews were conducted with thirty men and women of Black-African (n = 5), Black-Caribbean (n = 5), South Asian (n = 10) and White British (n = 10) descent. Participants were eligible for screening, but had not necessarily been invited for colonoscopy. All interviews were conducted in the participant's first language and were assessed using Framework-analysis, in line with a conceptual framework developed from previous interviews with healthcare professionals. RESULTS: Five thematic groups of barriers and facilitators were developed: 'Locus of control', 'Cultural attitudes and beliefs', 'Individual beliefs, knowledge and personal experiences with colonoscopy and cancer', 'Reliance on family and friends' and 'Health concerns'. Differences were observed, between ethnic groups, for: 'Locus of control', 'Cultural attitudes and beliefs' and 'Reliance on family and friends'. Black and South Asian participants frequently described the decision to attend colonoscopy as lying with 'God' (Muslims, specifically), 'the doctor', or 'family' (Locus of control). Black and South Asian participants also reported relying on friends and family for 'language, transport and emotional support' (Reliance on family and friends). Black-African participants, specifically, described cancer as 'socially taboo' (Cultural attitudes and beliefs). CONCLUSIONS: The results highlight several targets for culturally-tailored interventions to make colonoscopy more equitable.

Elucidating the role of the kinase activity of endothelial cell focal adhesion kinase in angiocrine signalling and tumour growth.

A common limitation of cancer treatments is chemotherapy resistance. We have previously identified that endothelial cell (EC)-specific deletion of focal adhesion kinase (FAK) sensitises tumour cells to DNA-damaging therapies, reducing tumour growth in mice. The present study addressed the kinase activity dependency of EC FAK sensitisation to the DNA-damaging chemotherapeutic drug, doxorubicin. FAK is recognised as a therapeutic target in tumour cells, leading to the development of a range of inhibitors, the majority being ATP competitive kinase inhibitors. We demonstrate that inactivation of EC FAK kinase domain (kinase dead; EC FAK-KD) in established subcutaneous B16F0 tumours improves melanoma cell sensitisation to doxorubicin. Doxorubicin treatment in EC FAK-KD mice reduced the percentage change in exponential B16F0 tumour growth further than in wild-type mice. There was no difference in tumour blood vessel numbers, vessel perfusion or doxorubicin delivery between genotypes, suggesting a possible angiocrine effect on the regulation of tumour growth. Doxorubicin reduced perivascular malignant cell proliferation, while enhancing perivascular tumour cell apoptosis and DNA damage in tumours grown in EC FAK-KD mice 48 h after doxorubicin injection. Human pulmonary microvascular ECs treated with the pharmacological FAK kinase inhibitors defactinib, PF-562,271 or PF-573,228 in combination with doxorubicin also reduced cytokine expression levels. Together, these data suggest that targeting EC FAK kinase activity may alter angiocrine signals that correlate with improved acute tumour cell chemosensitisation. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Outcomes of thrombus aspiration during primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Previous large multi-centre randomised controlled trials have not provided clear benefit with routine intracoronary thrombus aspiration (TA) as an adjunct to primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). AIM: To determine whether there is a difference in outcomes with the use of manual TA prior to PCI, compared with PCI alone in a cohort of patients with STEMI. METHODS: We analysed data from 6270 consecutive patients undergoing primary PCI for STEMI prospectively enrolled in the Melbourne Interventional Group registry between 2007 and 2018. Multivariable analysis was performed to determine predictors of 30-day major adverse cardiovascular and cerebrovascular events (MACCE) and long-term mortality. RESULTS: We compared 1621 (26%) patients undergoing primary PCI with TA to 4649 (74%) patients undergoing PCI alone. Male gender (81% vs 78%; P < 0.01), younger age (61 vs 63 years; P = 0.03), GP-IIb/IIIa use (76% vs 58%, P < 0.01), and current smoking (40% vs 36%; P < 0.01) were more common in the TA group. TA was more likely to be used in patients with complex lesions (83% vs 66%; P < 0.01) with TIMI 0 flow (77% vs 56%; P < 0.01). No significant difference in post-procedural TIMI flow, stroke, 30-day mortality, or long-term mortality were identified. Multivariable analysis demonstrated a reduction in 30-day MACCE (hazard ratio (HR) 0.75; confidence interval (CI) 0.63-0.89; P < 0.01) in the TA group, but was not associated with long-term mortality (HR 0.98; CI 0.85-1.1; P = 0.73). CONCLUSION: The use of TA in patients undergoing primary PCI for STEMI was not associated with improved short or long-term mortality when compared with PCI alone.

Impact of prehospital opioid dose on angiographic and clinical outcomes in acute coronary syndromes.

BACKGROUND: An adverse interaction whereby opioids impair and delay the gastrointestinal absorption of oral P2Y12 inhibitors has been established, however the clinical significance of this in acute coronary syndrome (ACS) is uncertain. We sought to characterise the relationship between prehospital opioid dose and clinical outcomes in patients with ACS. METHODS: Patients given opioid treatment by emergency medical services (EMS) with ACS who underwent percutaneous coronary intervention (PCI) between 1 January 2014 and 31 December 2018 were included in this retrospective cohort analysis using data linkage between the Ambulance Victoria, Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Patients with cardiogenic shock, out-of-hospital cardiac arrest and fibrinolysis were excluded. The primary end point was the risk-adjusted odds of 30-day major adverse cardiac events (MACE) between patients who received opioids and those that did not. RESULTS: 10 531 patients were included in the primary analysis. There was no significant difference in 30-day MACE between patients receiving opioids and those who did not after adjusting for key patient and clinical factors. Among patients with ST-elevation myocardial infarction (STEMI), there were significantly more patients with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow pre-PCI in a subset of patients with high opioid dose versus no opioids (56% vs 25%, p<0.001). This remained significant after adjusting for known confounders with a higher predicted probability of TIMI 0/1 flow in the high versus no opioid groups (33% vs 11%, p<0.001). CONCLUSIONS: Opioid use was not associated with 30-day MACE. There were higher rates of TIMI 0/1 flow pre-PCI in patients with STEMI prescribed opioids. Future prospective research is required to verify these findings and investigate alternative analgesia for ischaemic chest pain.

Long-Term Valve Durability in Patients Undergoing Transcatheter Aortic Valve Implantation.

AIMS: To evaluate the long-term incidence of structural valve deterioration (SVD) in patients who underwent transcatheter aortic valve implantation (TAVI). METHOD AND RESULTS: Between 2008 and 2018, 693 underwent TAVI at two centres. Four hundred and twenty-one (421) patients (mean age 83.6±6.0 yrs) survived for ≥2 years post TAVI and had at least two consecutive transthoracic echocardiographies (TTEs) with the latest TTE no less than 2 years after TAVI, and were therefore included in the analysis for SVD. Median follow-up was 4.7 (3.6-6.0) years and median echocardiography follow-up 3 (3.0-4.0) years. All-cause mortality was 30.9% (130) with a median time to death of 4.1 (3.0-5.6) years. The cumulative incidence of SVD increased from 1.7% (95% CI, 0.4-2.9) at 3 years to 3.5% (95% CI, 1.5-5.8) at 5 years and 4.7% (95% CI, 1.6-7.9) at 10 years. The overall median time to SVD was 3 (2-4) years. Twelve (12) patients demonstrated SVD stage 2, and 1 patient stage 3. No SVD required re-intervention. All other patients showed no significant changes in valve parameters over time. CONCLUSIONS: Structural valve deterioration is an uncommon event, occurring in 5% over a total follow-up of 10 years. Most patients show stable valve parameters. However, the analysis is limited by the loss of follow-up (owing to patient mortality), which renders extrapolation of the data to a younger patient population difficult.

Sex Differences in Pharmacotherapy and Long-Term Outcomes in Patients With Ischaemic Heart Disease and Comorbid Left Ventricular Dysfunction.

BACKGROUND: Left ventricular (LV) dysfunction and ischaemic heart disease (IHD) are common among women. However, women tend to present later and are less likely to receive guideline-directed medical therapy (GDMT) compared with men. METHODS: We analysed prospectively collected data (2005-2018) from a multicentre registry on GDMT 30 days after percutaneous coronary intervention in 13,015 patients with LV ejection fraction <50%. Guideline-directed medical therapy was defined as beta blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker±mineralocorticoid receptor antagonist. Long-term mortality was determined by linkage with the Australian National Death Index. RESULTS: Women represented 20% (2,634) of the total cohort. Mean age was 65±12 years. Women were on average >5 years, with higher body mass index and higher rates of hypertension, diabetes, renal dysfunction, prior stroke, and rheumatoid arthritis. Guideline-directed medical therapy was similar between sexes (73% vs 72%; p=0.58), although women were less likely to be on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80% vs 82%; p=0.02). Women were less likely to be on statin therapy (p<0.001) or a second antiplatelet agent (p=0.007). Women had higher unadjusted long-term mortality (25% vs 19%; p<0.001); however, there were no differences in long-term mortality between sexes on adjusted analysis (hazard ratio 0.99; 95% confidence interval 0.87-1.14; p=0.94). CONCLUSIONS: Rates of GDMT for LV dysfunction were high and similar between sexes; however, women were less likely to be on appropriate IHD secondary prevention. The increased unadjusted long-term mortality in women was attenuated in adjusted analysis, which highlights the need for optimisation of baseline risk to improve long-term outcomes of women with IHD and comorbid LV dysfunction.

Harmonising Individual Patient Level Cardiac Registry Data Across the Asia Pacific Region-A Feasibility Study of In-Hospital Outcomes of STEMI Patients From the Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) Network.

OBJECTIVE: The Asia-Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration was established to inform on percutaneous coronary intervention (PCI) in the Asia-Pacific Region. Our aims were to (i) determine the operational requirements to assemble an international individual patient dataset and validate the processes of governance, data quality and data security, and subsequently (ii) describe the characteristics and outcomes for ST-elevation myocardial infarction (STEMI) patients undergoing PCI in the ASPECT registry. METHODS: Seven (7) ASPECT members were approached to provide a harmonised anonymised dataset from their local registry. Patient characteristics were summarised and associations between the characteristics and in-hospital outcomes for STEMI patients were analysed. RESULTS: Six (6) participating sites (86%) provided governance approvals for the collation of individual anonymised patient data from 2015 to 2017. Five (5) sites (83%) provided >90% of agreed data elements and 68% of the collated elements had <10% missingness. From the registry (n=12,620), 84% were male. The mean age was 59.2±12.3 years. The Malaysian cohort had a high prevalence of previous myocardial infarction (34%), almost twice that of any other sites (p<0.001). Adverse in-hospital outcomes were the lowest in Hong Kong whilst in-hospital mortality varied from 2.7% in Vietnam to 7.9% in Singapore. CONCLUSIONS: Governance approvals for the collation of individual patient anonymised data was achieved with a high level of data alignment. Secure data transfer process and repository were established. Patient characteristics and presentation varied significantly across the Asia-Pacific region with this likely to be a major predictor of variations in the clinical outcomes observed across the region.

The projected impact of the COVID-19 lockdown on breast cancer deaths in England due to the cessation of population screening: a national estimation.

BACKGROUND: Population breast screening services in England were suspended in March 2020 due to the COVID-19 pandemic. Here, we estimate the number of breast cancers whose detection may be delayed because of the suspension, and the potential impact on cancer deaths over 10 years. METHODS: We estimated the number and length of screening delays from observed NHS Breast Screening System data. We then estimated additional breast cancer deaths from three routes: asymptomatic tumours progressing to symptomatically diagnosed disease, invasive tumours which remain screen-detected but at a later date, and ductal carcinoma in situ (DCIS) progressing to invasive disease by detection. We took progression rates, prognostic characteristics, and survival rates from published sources. RESULTS: We estimated that 1,489,237 women had screening delayed by around 2-7 months between July 2020 and June 2021, leaving 745,277 outstanding screens. Depending on how quickly this backlog is cleared, around 2500-4100 cancers would shift from screen-detected to symptomatic cancers, resulting in 148-452 additional breast cancer deaths. There would be an additional 164-222 screen-detected tumour deaths, and 71-97 deaths from DCIS that progresses to invasive cancer. CONCLUSIONS: An estimated 148-687 additional breast cancer deaths may occur as a result of the pandemic-related disruptions. The impact depends on how quickly screening services catch up with delays.

Impact of changes to the interscreening interval and faecal immunochemical test threshold in the national bowel cancer screening programme in England: results from the FIT pilot study.

INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) faces endoscopy capacity challenges from the COVID-19 pandemic and plans to lower the screening starting age. This may necessitate modifying the interscreening interval or threshold. METHODS: We analysed data from the English Faecal Immunochemical Testing (FIT) pilot, comprising 27,238 individuals aged 59-75, screened for colorectal cancer (CRC) using FIT. We estimated screening sensitivity to CRC, adenomas, advanced adenomas (AA) and mean sojourn time of each pathology by faecal haemoglobin (f-Hb) thresholds, then predicted the detection of these abnormalities by interscreening interval and f-Hb threshold. RESULTS: Current 2-yearly screening with a f-Hb threshold of 120 µg/g was estimated to generate 16,092 colonoscopies, prevent 186 CRCs, detect 1142 CRCs, 7086 adenomas and 4259 AAs per 100,000 screened over 15 years. A higher threshold at 180 µg/g would reduce required colonoscopies to 11,500, prevent 131 CRCs, detect 1077 CRCs, 4961 adenomas and 3184 AAs. A longer interscreening interval of 3 years would reduce required colonoscopies to 10,283, prevent 126 and detect 909 CRCs, 4796 adenomas and 2986 AAs. CONCLUSION: Increasing the f-Hb threshold was estimated to be more efficient than increasing the interscreening interval regarding overall colonoscopies per screen-benefited cancer. Increasing the interval was more efficient regarding colonoscopies per cancer prevented.

Benefits and harms of annual, biennial, or triennial breast cancer mammography screening for women at average risk of breast cancer: a systematic review for the European Commission Initiative on Breast Cancer (ECIBC).

BACKGROUND: Although mammography screening is recommended in most European countries, the balance between the benefits and harms of different screening intervals is still a matter of debate. This review informed the European Commission Initiative on Breast Cancer (BC) recommendations. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify RCTs, observational or modelling studies, comparing desirable (BC deaths averted, QALYs, BC stage, interval cancer) and undesirable (overdiagnosis, false positive related, radiation related) effects from annual, biennial, or triennial mammography screening in women of average risk for BC. We assessed the certainty of the evidence using the GRADE approach. RESULTS: We included one RCT, 13 observational, and 11 modelling studies. In women 50-69, annual compared to biennial screening may have small additional benefits but an important increase in false positive results; triennial compared to biennial screening may have smaller benefits while avoiding some harms. In younger women (aged 45-49), annual compared to biennial screening had a smaller gain in benefits and larger harms, showing a less favourable balance in this age group than in women 50-69. In women 70-74, there were fewer additional harms and similar benefits with shorter screening intervals. The overall certainty of the evidence for each of these comparisons was very low. CONCLUSIONS: In women of average BC risk, screening intervals have different trade-offs for each age group. The balance probably favours biennial screening in women 50-69. In younger women, annual screening may have a less favourable balance, while in women aged 70-74 years longer screening intervals may be more favourable.

Selection of eligible participants for screening for lung cancer using primary care data.

Lung cancer screening is effective if offered to people at increased risk of the disease. Currently, direct contact with potential participants is required for evaluating risk. A way to reduce the number of ineligible people contacted might be to apply risk-prediction models directly to digital primary care data, but model performance in this setting is unknown. METHOD: The Clinical Practice Research Datalink, a computerised, longitudinal primary care database, was used to evaluate the Liverpool Lung Project V.2 (LLPv2) and Prostate Lung Colorectal and Ovarian (modified 2012) (PLCOm2012) models. Lung cancer occurrence over 5-6 years was measured in ever-smokers aged 50-80 years and compared with 5-year (LLPv2) and 6-year (PLCOm2012) predicted risk. RESULTS: Over 5 and 6 years, 7123 and 7876 lung cancers occurred, respectively, from a cohort of 842 109 ever-smokers. After recalibration, LLPV2 produced a c-statistic of 0.700 (0.694-0.710), but mean predicted risk was over-estimated (predicted: 4.61%, actual: 0.9%). PLCOm2012 showed similar performance (c-statistic: 0.679 (0.673-0.685), predicted risk: 3.76%. Applying risk-thresholds of 1% (LLPv2) and 0.15% (PLCOm2012), would avoid contacting 42.7% and 27.4% of ever-smokers who did not develop lung cancer for screening eligibility assessment, at the cost of missing 15.6% and 11.4% of lung cancers. CONCLUSION: Risk-prediction models showed only moderate discrimination when applied to routinely collected primary care data, which may be explained by quality and completeness of data. However, they may substantially reduce the number of people for initial evaluation of screening eligibility, at the cost of missing some lung cancers. Further work is needed to establish whether newer models have improved performance in primary care data.

Higher Adenoma Detection Rates at Screening Associated With Lower Long-Term Colorectal Cancer Incidence and Mortality.

BACKGROUND & AIMS: Detection and removal of adenomas reduces colorectal cancer (CRC) risk. The impact of adenoma detection rates (ADRs) on long-term CRC incidence and mortality is unknown. We investigated this using data from the UK Flexible Sigmoidoscopy Screening Trial. METHODS: Of 167,882 UK Flexible Sigmoidoscopy Screening Trial participants, 40,085 were in the intervention arm and underwent flexible sigmoidoscopy screening at 13 trial centers. The median follow-up time was 17 years. At each center, 1 endoscopist performed most flexible sigmoidoscopies. Multivariable logistic regression was used to classify centers into high-, intermediate-, and low-detector groups based on their main endoscopist's ADR. We calculated the incidence and mortality of distal and all-site CRC, and estimated hazard ratios (HRs) with 95% CIs using Cox regression. RESULTS: Five, 4, and 4 centers, respectively, were classified into the high-detector, intermediate-detector, and low-detector groups. The average ADRs in each respective group were 15%, 12%, and 9%. Distal CRC incidence and mortality were reduced among those screened compared with controls in all groups, and effects of screening varied significantly by detector ranking, with larger reductions in incidence and mortality seen in the high-detector group (incidence: HR, 0.34; 95% CI, 0.27-0.42; mortality: HR, 0.22, 95% CI, 0.13-0.37) than in the low-detector group (incidence: HR, 0.55; 95% CI, 0.44-0.68; mortality: HR, 0.54; 95% CI, 0.34-0.86). Similar results were observed for all-site CRC, with larger effects seen in the high-detector (incidence: HR, 0.58; 95% CI, 0.50-0.67; mortality: HR, 0.52; 95% CI, 0.39-0.69) than in the low-detector group (incidence: HR, 0.72; 95% CI, 0.61-0.85; mortality: HR, 0.68; 95% CI, 0.51-0.92), although the heterogeneity was not statistically significant. CONCLUSIONS: Higher ADRs at screening provide greater long-term protection against CRC incidence and mortality. Isrctn.org, number: ISRCTN28352761.

A Randomized Trial Comparing Breast Cancer Incidence and Interval Cancers after Tomosynthesis Plus Mammography versus Mammography Alone.

Background Adding digital breast tomosynthesis (DBT) to digital mammography (DM) improves breast cancer screening sensitivity, but how this impacts mortality and other end points is unknown. Purpose To compare interval and overall breast cancer incidence after screening with DBT plus DM versus DM alone. Materials and Methods In this prospective trial (RETomo), women attending screening were randomized to one round of DBT plus DM (experimental arm) or to DM (control arm). All were then rescreened with DM after 12 months (women aged 45-49 years) or after 24 months (50-69 years). The primary outcome was interval cancer incidence. Cumulative incidence up to the subsequent screening round plus 9 months (21- and 33-month follow-up for women aged 45-49 and 50-69, respectively) was also reported. Ductal carcinomas in situ are included. Subgroup analyses by age and breast density were conducted; 95% CIs computed according to binomial distribution are reported. Results Baseline cancer detection was higher in the DBT plu DM arm than DM arm (101 of 13 356 women vs 61 of 13 521 women; relative detection, 1.7 [95% CI: 1.2, 2.3]). The mean age ± standard deviation for the women in both arms was 55 years ± 7. Interval cancer incidence was similar in the two arms (21 vs 22 cancers; relative incidence, 0.97 [95% CI: 0.53, 1.8]). Cumulative incidence remained higher in the DBT plus DM arm in women over 50 (153 vs 124 cancers; relative incidence, 1.2 [95% CI: 0.99, 1.6]), while it was similar in the two arms in women aged 45-49 (36 vs 41 cancers; relative incidence, 0.89 [95% CI: 0.57, 1.4]). Conclusion In women younger than 50 years, the benefit of early diagnosis seemed to be appreciable, while for women over age 50, the higher sensitivity of tomosynthesis plus mammography was not matched by a subsequent reduction in cancers at the next screening examination or in the intervening interval. Clinical trial registration no. NCT02698202 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Ray in this issue.

Long-term mortality in asymptomatic patients with stable ischemic heart disease undergoing percutaneous coronary intervention.

OBJECTIVES: Patients with stable ischemic heart disease (SIHD) may present with a variety of symptoms including typical angina, angina equivalents such as dyspnea or no symptoms. We sought to determine whether symptom status affects periprocedural safety and long-term mortality in patients undergoing PCI. METHODS: Prospectively enrolled consecutive patients undergoing PCI for SIHD at six hospitals in Australia between 2005 to 2018 as part of the Melbourne Interventional Group registry. Symptom status was recorded at the time of PCI and patients undergoing staged PCI were excluded. RESULTS: Overall, 11,730 patients with SIHD were followed up for a median period of 5 years (maximum 14.0 years, interquartile range 2.2-9.0 years) with 1,317 (11.2%) being asymptomatic. Asymptomatic patients were older, and more likely to be male, have triple-vessel disease, with multiple comorbidities including renal failure, diabetes and heart failure (all P < .01). These patients had significantly higher rates of periprocedural complications and major adverse cardiovascular events at 30-days. Long-term mortality was significantly higher in asymptomatic patients (27.2% vs 18.0%, P < .001). On cox regression for long-term mortality, after adjustment for more important clinical variables, asymptomatic status was an independent predictor (Hazard ratio (HR) 1.39 95% CI 1.16-1.66, P < .001). CONCLUSIONS: In a real-world cohort of patients undergoing revascularization for SIHD, absence of symptoms was associated with higher rates of periprocedural complications and, after adjustment for more important clinical variables, was an independent predictor of long-term mortality. As the primary goal of revascularization in SIHD remains angina relief, the appropriateness of PCI in the absence of symptoms warrants justification.

Characteristics and outcomes of unsuccessful percutaneous coronary intervention.

OBJECTIVES: To examine predictors and outcomes of unsuccessful percutaneous coronary intervention (PCI) cases in a contemporary Australian registry cohort. BACKGROUND: With improvements in techniques and pharmacotherapy in PCI, more complex lesions in older patients are now being attempted. In the context of PCI performance assessment, there are limited data regarding the characteristics and outcomes of unsuccessful PCI. METHOD: We prospectively collected data on patients undergoing single-lesion PCI between 2013 and 2017 who were enrolled in the multi-center Victorian Cardiac Outcomes Registry. Procedures were divided into two groups by whether or not PCI was deemed successful at the end of the procedure using a pre-specified definition. RESULTS: There were 34,383 single-lesion PCI performed, of which 18,644 (54.2%) were for acute coronary syndromes. Of the study cohort, 2080 patients (6.0%) had an unsuccessful PCI - these patients were older, more likely to have previous stroke, PCI, severe left ventricular dysfunction and chronic kidney disease (all p < 0.001). The procedure was also more likely to be performed for stable angina (p < 0.001). Chronic total occlusion PCI made up 31% of unsuccessful PCI cases. Unsuccessful PCI was itself associated with higher in-hospital and 30-day mortality and MACE (all p < 0.001). 4.9% of unsuccessful PCIs led to unplanned in-hospital bypass surgery (compared to 0.2% in successful PCIs, p < 0.001). CONCLUSION: Our study highlights that even in contemporary PCI practice, more than 1 in 20 PCI attempts are unsuccessful. Lack of procedural success has a strong influence on patient outcomes. Monitoring rates of unsuccessful cases is an important quality assurance tool.

Sex differences in prehospital analgesia in patients presenting with acute coronary syndromes and their association with clinical outcomes.

OBJECTIVES: This study examined if sex differences in prehospital pain scores, opioid administration, and clinical outcomes exist in acute coronary syndrome (ACS) patients. BACKGROUND: Sex differences persist in ACS presentation, management, and outcomes. The impact of sex differences on prehospital pain management of ACS with opioids is unknown. METHODS: Patients presenting with ACS via ambulance (2014-2018) that underwent percutaneous coronary intervention (PCI) were prospectively collected via the Victorian Cardiac Outcomes Registry and Melbourne Interventional Group, linked to the Ambulance Victoria database. The primary outcome was 30-day major adverse cardiac events (MACE). Secondary outcomes were descriptive analyses of prehospital pain score, intravenous morphine equivalent analgesic dosing, plus predictors of MACE and thrombolysis in myocardial infarction (TIMI) 0-1 flow pre-PCI. RESULTS: A total of 10,547 patients were included (female: 2775 [26%]). Opioids were administered to 1585 (57%) females, 5068 (65%) males (p < 0.001). Adjusted 30-day MACE was similar between opioid groups in both sexes (female: odds ratio [OR]: 1.21, confidence interval [CI] 0.82-1.79, p = 0.34; male: OR: 0.89, CI: 0.68-1.16, p = 0.40). Median pain score at presentation was 6 (interquartile range [IQR]: 4, 8) for both sexes. Median opioid dose was 2.5 mg (IQR: 0, 10) in females and 5 mg (IQR: 0, 10) in males (p < 0.001), with similar pain relief achieved. Adjusted rates of TIMI 0-1 pre-PCI were higher in patients administered opioids (female: OR 2.9, CI: 2.07-4.07, p < 0.001; male: OR: 2.67, CI: 2.19-3.25, p < 0.001). CONCLUSIONS: Female patients undergoing PCI received less opioid analgesia, but no sex differences in prehospital pain scores were seen. Opioid administration was associated with impaired antegrade flow in the culprit artery in both sexes, but not short-term MACE. Trials evaluating nonopioid analgesics in ACS are needed.