Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer.

Importance: The current quality performance measure for colorectal cancer (CRC) screening is limited to initial screening. Despite low rates, there is no measure for appropriate follow-up with colonoscopy after receipt of an abnormal result of a stool-based screening test (SBT) for CRC. A quality performance measure is needed. Objective: To develop and test a quality performance measure for follow-up colonoscopy within 6 months of an abnormal result of an SBT for CRC. Design, Setting, and Participants: This retrospective quality improvement study examined data from January 1, 2016, to December 31, 2020, with 2018 plus 6 months of follow-up as the primary measurement period to verify performance rates, specify a potential measure, and test for validity, reliability, and feasibility. The Optum Labs Data Warehouse (OLDW), a deidentified database of health care claims and clinical data, was accessed. The OLDW contains longitudinal health information on enrollees and patients, representing a diverse mixture of ages and geographic regions across the US. For the database study, adults from 38 health care organizations (HCOs) aged 50 to 75 years who completed an initial CRC SBT with an abnormal result were observed to determine follow-up colonoscopy rates within 6 months. Rates were stratified by race, ethnicity, sex, insurance, and test modality. Three HCOs participated in the feasibility field testing. Data were analyzed from June 1, 2022, to May 31, 2023. Main Outcome and Measures: The primary outcome consisted of follow-up colonoscopy rates following an abnormal SBT result for CRC. Reliability statistics were also calculated across HCOs, race, ethnicity, and measurement year. Results: Among 20 581 adults (48.6% men and 51.4% women; 307 [1.5%] Asian, 492 [7.2%] Black, 644 [3.1%] Hispanic, and 17 705 [86.0%] White; mean [SD] age, 63.6 [7.1] years) in 38 health systems, 47.9% had a follow-up colonoscopy following an abnormal SBT result for CRC within 6 months. There was significant variation between HCOs. Notably, significantly fewer Black patients (37.1% [95% CI, 34.6%-39.5%]) and patients with Medicare (49.2% [95% CI, 47.7%-50.6%]) or Medicaid (39.2% [95% CI, 36.3%-42.1%]) insurance received a follow-up colonoscopy. A quality performance measure that tracks rates of follow-up within 6 months of an abnormal SBT result was observed to be feasible, valid, and reliable, with a median reliability statistic between HCOs of 94.5% (range, 74.3%-99.7%). Conclusions and Relevance: The findings of this observational study of 20 581 adults suggest that a measure of follow-up colonoscopy within defined periods after an abnormal result of an SBT test for CRC is warranted based on low current performance rates and would be feasible to collect by health systems and produce valid, reliable results.

Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. METHODS AND RESULTS: The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. CONCLUSIONS: The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Associations between Cerebrovascular Function and the Expression of Genes Related to Endothelial Function in Hormonal Migraine.

There is evidence to suggest that hormonal migraine is associated with altered cerebrovascular function. We aimed to investigate whether the expression of genes related to endothelial function in venous blood (1) might influence cerebrovascular function, (2) differs between hormonal migraineur and non-migraineur women, and (3) changes following resveratrol supplementation. This study utilised data obtained from 87 women (59 hormonal migraineurs and 28 controls) where RNA from venous blood was used to quantify gene expression and transcranial Doppler ultrasound was used to evaluate cerebrovascular function. Spearman's correlation analyses were performed between gene expression, cerebrovascular function, and migraine-related disability. We compared the expression of genes associated with endothelial function between migraineurs and non-migraineurs, and between resveratrol and placebo. The expression of several genes related to endothelial function was associated with alterations in cerebrovascular function. Notably, the expression of CALCA was associated with increased neurovascular coupling capacity (p = 0.013), and both CALCA (p = 0.035) and VEGF (p = 0.014) expression were associated with increased cerebral blood flow velocity in the overall study population. Additionally, VCAM1 expression correlated with decreased pulsatility index (a measure of cerebral arterial stiffness) (p = 0.009) and headache impact test-6 scores (p = 0.007) in the migraineurs. No significant differences in gene expression were observed between migraineurs and controls, or between placebo and resveratrol treatments in migraineurs. Thus, altering the expression of genes related to endothelial function may improve cerebrovascular function and decrease migraine-related disability.

Colorectal cancer screening test exposure patterns in US adults 45 to 49 years of age, 2019-2021.

Several organizations now recommend that individuals at average risk for colorectal cancer (CRC) begin screening at 45 rather than 50 years of age. We present contemporary estimates of CRC screening in newly eligible adults aged 45 to 49 years between 2019 and 2021. Nationally representative prevalence estimates and population number screened were estimated based on the National Health Interview Survey. A logistic regression model assessed CRC screening prevalence differences by survey year and sociodemographic characteristics. In 2021, 19.7%-that is, fewer than 4 million of the eligible 19 million adults aged 45 to 49 years-were up-to-date on CRC screening. Screening was lowest in those who were uninsured (7.6%), had less than a high school diploma (15.4%), and Asian (13.1%). Additionally, fecal occult blood test and/or fecal immunochemical testing was underused, with only 2.4% (<460 000 people) reporting being up-to-date with screening using this modality in 2021. CRC screening in eligible young adults remains low. Concerted efforts to improve screening are warranted, particularly in underserved populations.

Lung cancer statistics, 2023.

Despite decades of declining mortality rates, lung cancer remains the leading cause of cancer death in the United States. This article examines lung cancer incidence, stage at diagnosis, survival, and mortality using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Over the past 5 years, declines in lung cancer mortality became considerably greater than declines in incidence among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually), reflecting absolute gains in 2-year relative survival of 1.4% annually. Improved outcomes likely reflect advances in treatment, increased access to care through the Patient Protection and Affordable Care Act, and earlier stage diagnosis; for example, compared with a 4.6% annual decrease for distant-stage disease incidence during 2013-2019, the rate for localized-stage disease rose by 3.6% annually. Localized disease incidence increased more steeply in states with the highest lung cancer screening prevalence (by 3%-5% annually) than in those with the lowest (by 1%-2% annually). Despite progress, disparities remain. For example, Native Americans have the highest incidence and the slowest decline (less than 1% annually among men and stagnant rates among women) of any group. In addition, mortality rates in Mississippi and Kentucky are two to three times higher than in most western states, largely because of elevated historic smoking prevalence that remains. Racial and geographic inequalities highlight longstanding opportunities for more concerted tobacco-control efforts targeted at high-risk populations, including improved access to smoking-cessation treatments and lung cancer screening, as well as state-of-the-art treatment.

Benefit-to-radiation-risk of low-dose computed tomography lung cancer screening.

BACKGROUND: The US National Lung Screening Trial (NLST) and Dutch-Belgian NELSON randomized controlled trials have shown significant mortality reductions from low-dose computed tomography (CT) lung cancer screening (LCS). NLST, ITALUNG, and COSMOS trials have provided detailed dosimetry data for LCS. METHODS: LCS trial mortality benefit results, organ dose and effective dose data, and Biological Effects of Ionizing Radiation, Report VII (BEIR VII) organ dose-to-cancer-mortality risk data are used to estimate benefit-to-radiation-risk ratios of the NLST, ITALUNG, and COSMOS trials. Data from those trials also are used to estimate benefit-to-radiation-risk ratios for longer-term LCS corresponding to scenarios recommended by United States Preventive Services Task Force and the American Cancer Society. RESULTS: Including only screening doses, NLST benefit-to-radiation-risk ratios are 12:1 for males, 19:1 for females, and 16:1 overall. Including both screening and estimated follow-up doses, benefit-to-radiation-risk ratios for NLST are 9:1 for males, 13:1 for females, and 12:1 overall. For the ITALUNG trial, the benefit-to-radiation-risk ratio is 58-63:1. For the COSMOS trial, assuming sex-specific mortality benefits like those of the NELSON trial, the benefit-to-radiation-risk ratio is 23:1. Assuming a conservative 20% mortality benefit, annual screening in people 50-79 years old with a 20+ pack-year history of smoking has benefit-to-radiation-risk ratios of 23:1 (with follow-up doses adding 40% to screening doses) to 29:1 (with follow-up adding 10%) based on COSMOS dose data. CONCLUSIONS: Based on linear, no threshold BEIR VII dose-risk estimates, benefit-to-radiation-risk ratios for LCS are highly favorable. Results emphasize the importance of using modern CT technologies, maintaining low diagnostic follow-up rates, and minimizing both screening and diagnostic follow-up doses. PLAIN LANGUAGE SUMMARY: The benefits of lung cancer screening significantly outweigh estimates of future harms associated with exposure to radiation during screening and diagnostic follow-up examinations. Our findings emphasize the importance of lung cancer screening practices using state-of-the-art computed tomography scanners and specialized low-dose lung screening and diagnostic follow-up techniques.

Assessing the impact of increasing lung screening eligibility by relaxing the maximum years-since-quit threshold: A simulation modeling study.

BACKGROUND: In 2021, the US Preventive Services Task Force expanded its lung screening recommendation to include persons aged 50-80 years who had ever smoked and had at least 20 pack-years of exposure and less than 15 years since quitting (YSQ). However, studies have suggested that screening persons who formerly smoked with longer YSQ could be beneficial. METHODS: The authors used two validated lung cancer models to assess the benefits and harms of screening using various YSQ thresholds (10, 15, 20, 25, 30, and no YSQ) and the age at which screening was stopped. The impact of enforcing the YSQ criterion only at entry, but not at exit, also was evaluated. Outcomes included the number of screens, the percentage ever screened, screening benefits (lung cancer deaths averted, life-years gained), and harms (false-positive tests, overdiagnosed cases, radiation-induced lung cancer deaths). Sensitivity analyses were conducted to evaluate the effect of restricting screening to those who had at least 5 years of life expectancy. RESULTS: As the YSQ criterion was relaxed, the number of screens and the benefits and harms of screening increased. Raising the age at which to stop screening age resulted in additional benefits but with more overdiagnosis, as expected, because screening among those older than 80 years increased. Limiting screening to those who had at least 5 years of life expectancy would maintain most of the benefits while considerably reducing the harms. CONCLUSIONS: Expanding screening to persons who formerly smoked and have greater than 15 YSQ would result in considerable increases in deaths averted and life-years gained. Although additional harms would occur, these could be moderated by ensuring that screening is restricted to only those with reasonable life expectancy.

Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

The Importance of Outcomes Ascertainment for Accurate Assessment of the Mammography Screening Cancer Detection Rate: A Simulation Study.

PURPOSE: Cancer detection rate (CDR), an important metric in the mammography screening audit, is designed to ensure adequate sensitivity. Most practices use biopsy results as the reference standard; however, commonly ascertainment of biopsy results is incomplete. We used simulation to determine the relationship between the cancer ascertainment rate of biopsy (AR-biopsy), CDR estimation, and associated error rates in classifying whether practices and radiologists meet the established ACR benchmark of 2.5 per 1,000. MATERIALS AND METHODS: We simulated screening mammography volume, number of cancers detected, and CDR, using negative binomial and beta-binomial distributions, respectively. Simulations were performed at both the practice and radiologist level. Average CDR was based on linearly rescaling a published CDR by the AR-biopsy. CDR distributions were simulated for AR-biopsy between 5% and 100% in steps of five percentage points and were summarized with boxplots and smoothed histograms over the range of AR-biopsy, to quantify the proportion of practices and radiologists meeting the ACR benchmark at each level of AR-biopsy. RESULTS: Decreasing AR-biopsy led to an increasing probability of categorizing CDR performance as being below the ACR benchmark. Our simulation predicts that at the practice level, an AR-biopsy of 65% categorizes 17.6% below the benchmark (compared to 1.6% at an AR-biopsy of 100%), and at the radiologist level, an AR-biopsy of 65% categorizes 34.7% as being below the benchmark (compared to 11.6% at an AR-biopsy of 100%). CONCLUSIONS: Our simulation demonstrates that decreasing the AR-biopsy (in currently clinically relevant ranges) has the potential to artifactually lower the assessed CDR on both the practice and radiologist levels and may, in turn, increase the chance of erroneous categorization of underperformance per the ACR benchmark.

Beneficial effect of repeated participation in breast cancer screening upon survival.

OBJECTIVES: The benefit of mammography screening in reducing population mortality from breast cancer is well established. In this paper, we estimate the effect of repeated participation at scheduled screens on case survival. METHODS: We analysed incidence and survival data on 37,079 women from nine Swedish counties who had at least one to five invitation(s) to screening prior to diagnosis, and were diagnosed with breast cancer between 1992 and 2016. Of these, 4564 subsequently died of breast cancer. We estimated the association of survival with participation in up to the most recent five screens before diagnosis. We used proportional hazards regression to estimate the effect on survival of the number of scheduled screens in which subjects participated prior to the diagnosis of breast cancer. RESULTS: There was successively better survival with an increasing number of screens in which the subject participated. For a woman with five previous screening invitations who participated in all five, the hazard ratio was 0.28 (95% confidence interval (CI) 0.25-0.33, p < 0.0001) compared to a woman attending none (86.9% vs 68.9% 20-year survival). Following a conservative adjustment for potential self-selection factors, the hazard ratio was 0.34 (95% CI 0.26-0.43, p < 0.0001), an approximate three-fold reduction in the hazard of dying from breast cancer. CONCLUSION: For those women who develop breast cancer, regular prior participation in mammography screening confers significantly better survival.

Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer.

Low-dose computed tomography (LDCT) screening for lung cancer substantially reduces mortality from lung cancer, as revealed in randomized controlled trials and meta-analyses. This review is based on the ninth CT screening symposium of the International Association for the Study of Lung Cancer, which focuses on the major themes pertinent to the successful global implementation of LDCT screening and develops a strategy to further the implementation of lung cancer screening globally. These recommendations provide a 5-year roadmap to advance the implementation of LDCT screening globally, including the following: (1) establish universal screening program quality indicators; (2) establish evidence-based criteria to identify individuals who have never smoked but are at high-risk of developing lung cancer; (3) develop recommendations for incidentally detected lung nodule tracking and management protocols to complement programmatic lung cancer screening; (4) Integrate artificial intelligence and biomarkers to increase the prediction of malignancy in suspicious CT screen-detected lesions; and (5) standardize high-quality performance artificial intelligence protocols that lead to substantial reductions in costs, resource utilization and radiologist reporting time; (6) personalize CT screening intervals on the basis of an individual's lung cancer risk; (7) develop evidence to support clinical management and cost-effectiveness of other identified abnormalities on a lung cancer screening CT; (8) develop publicly accessible, easy-to-use geospatial tools to plan and monitor equitable access to screening services; and (9) establish a global shared education resource for lung cancer screening CT to ensure high-quality reading and reporting.

Antiviral Activity of Lenacapavir Against HIV-2 Isolates and Drug-resistant HIV-2 Mutants.

The activity of lenacapavir against HIV-1 has been extensively evaluated in vitro, but comparable data for HIV-2 are scarce. We determined the anti-HIV-2 activity of lenacapavir using single-cycle infections of MAGIC-5A cells and multicycle infections of a T cell line. Lenacapavir exhibited low-nanomolar activity against HIV-2, but was 11- to 14-fold less potent against HIV-2 in comparison to HIV-1. Mutations in HIV-2 that confer resistance to other antiretrovirals did not confer cross-resistance to lenacapavir. Although lenacapavir-containing regimens might be considered for appropriate patients with HIV-2, more frequent viral load and/or CD4 testing may be needed to assess clinical response.

A plea for more careful scholarship in reviewing evidence: the case of mammographic screening.

Objectives: To identify issues of principle and practice giving rise to misunderstandings in reviewing evidence, to illustrate these by reference to the Nordic Cochrane Review (NCR) and its interpretation of two trials of mammographic screening, and to draw lessons for future reviewing of published results. Methods: A narrative review of the publications of the Nordic Cochrane Review of mammographic screening (NCR), the Swedish Two-County Trial (S2C) and the Canadian National Breast Screening Study 1 and 2 (CNBSS-1 and CNBSS-2). Results: The NCR concluded that the S2C was unreliable, despite the review's complaints being shown to be mistaken, by direct reference to the original primary publications of the S2C. Repeated concerns were expressed by others about potential subversion of randomisation in CNBSS-1 and CNBSS-2; however, the NCR continued to rely heavily on the results of these trials. Since 2022, however, eyewitness evidence of such subversion has been in the public domain. Conclusions: An over-reliance on nominal satisfaction of checklists of criteria in systematic reviewing can lead to erroneous conclusions. This occurred in the case of the NCR, which concluded that mammographic screening was ineffective or minimally effective. Broader and more even-handed reviews of the evidence show that screening confers a substantial reduction in breast cancer mortality. Advances in knowledge: Those carrying out systematic reviews should be aware of the dangers of over-reliance on checklists and guidelines. Readers of systematic reviews should be aware that a systematic review is just another study, with the capability that all studies have of coming to incorrect conclusions. When a review seems to overturn the current position, it is essential to revisit the publications of the primary research.

Cancer Screening: Patient and Population Strategies.

Although cancer has been the second leading cause of death for close to 100 years, progress has been made in reducing cancer mortality and morbidity, with the adoption of high-quality screening tests and treatment advances delivered at earlier stages of diagnosis. To achieve the high cancer screening rates demonstrated by some practices, proven effective strategies need to be broadly adopted at both the patient and population levels. Factors affecting cancer screening test completion and approaches to improvement are described both generally and for breast, lung, cervical, colorectal, and prostate cancers. Closing the racial disparity gap is a critical component of reaching cancer screening and prevention goals.

Getting ready for prime time: Recommended adaptations of an Empathic Communication Skills training intervention to reduce lung cancer stigma for a national multi-center trial.

Building upon prior work developing and pilot testing a provider-focused Empathic Communication Skills (ECS) training intervention, this study sought feedback from key invested partners who work with individuals with lung cancer (i.e. stakeholders including scientific and clinical advisors and patient advocates) on the ECS training intervention. The findings will be used to launch a national virtually-delivered multi-center clinical trial that will examine the effectiveness and implementation of the evidence-based ECS training intervention to reduce patients' experience of lung cancer stigma. A 1-day, hybrid, key invested partners meeting was held in New York City in Fall 2021. We presented the ECS training intervention to all conference attendees (N = 25) to seek constructive feedback on modifications of the training content and platform for intervention delivery to maximize its impact. After participating in the immersive training, all participants engaged in a group discussion guided by semi-structured probes. A deductive thematic content analysis was conducted to code focus group responses into 12 distinct a priori content modification recommendations. Content refinement was suggested in 8 of the 12 content modification themes: tailoring/tweaking/refining, adding elements, removing elements, shortening/condensing content, lengthening/extending content, substituting elements, re-ordering elements, and repeating elements. Engagement and feedback from key invested multi-sector partner is a valuable resource for intervention content modifications. Using a structured format for refining evidence-based interventions can facilitate efforts to understand the nature of modifications required for scaling up interventions and the impact of these modifications on outcomes of interest. ClinicalTrials.gov Identifier: NCT05456841.

This study was done to get feedback from people who are involved with patients with lung cancer (PwLCs) including scientists, clinicians, and patient advocates on training in Empathic Communication Skills (ECS). The training is intended to reduce PwLCs experience of lung cancer stigma. The feedback is being used to help prepare for launching the training program in multiple cancer centers across the USA to test how well the training will work to reduce the stigma felt by PwLCs. A one-day, hybrid (in-person and virtual attendees) meeting was held in New York City in October 2021. We presented the original version of the ECS training program to all conference attendees (N = 25) to get feedback on modifications to improve the training program for the larger study planned at many cancer centers. After the training, all meeting attendees participated in a semi-structured group discussion. The content of the discussion was analyzed and sorted into 12 distinct categories that were defined before the meeting. Changes to the content were suggested in 8 of the 12 categories. These changes included tailoring/tweaking/refining, adding elements, removing elements, shortening/condensing content, lengthening/extending content, substituting elements, re-ordering elements, and repeating elements. Engaging and getting feedback from people involved in a topic is a good way to improve content and delivery of training materials.

Imaging biomarkers are underutilised but highly predictive prognostic factors for the more fatal breast cancer subtypes.

PURPOSE: The development and refinement of breast imaging modalities offer a wealth of diagnostic information such as imaging biomarkers, which are primarily the mammographic appearance of the various breast cancer subtypes. These are readily available preoperatively at the time of diagnosis and can enhance the prognostic value of currently used molecular biomarkers. In this study, we investigated the relative utility of the molecular and imaging biomarkers, both jointly and independently, when predicting long-term patient outcome according to the site of tumour origin. METHODS: We evaluated the association of imaging biomarkers and conventional molecular biomarkers, (ER, PR, HER-2, Ki67), separately and combined, with long-term patient outcome in all breast cancer cases having complete data on both imaging and molecular biomarkers (n = 2236) diagnosed in our Institute during the period 2008-2019. Large format histopathology technique was used to document intra- and intertumoural heterogeneity and select the appropriate foci for evaluating molecular biomarkers. RESULTS: The breast cancer imaging biomarkers were strongly predictive of long-term patient outcome. The molecular biomarkers were predictive of outcome only for unifocal acinar adenocarcinoma of the breast (AAB), but less reliable in the multifocal AAB cases due to variability of molecular biomarkers in the individual tumour foci. In breast cancer of mesenchymal origin (BCMO), conventionally termed classic invasive lobular carcinoma, and in cancers originating from the major lactiferous ducts (ductal adenocarcinoma of the breast, DAB), the molecular biomarkers misleadingly indicated favourable prognosis, whereas the imaging biomarkers in BCMO and DAB reliably indicated the high risk of breast cancer death. Among the 2236 breast cancer cases, BCMO and DAB comprised 21% of the breast cancer cases, but accounted for 45% of the breast cancer deaths. CONCLUSIONS: Integration of imaging biomarkers into the diagnostic workup of breast cancer yields a more precise, comprehensive and prognostically accurate diagnostic report. This is particularly necessary in multifocal AAB cases having intertumoural heterogeneity, in diffuse carcinomas (DAB and BCMO), and in cases with combined DAB and AAB. In such cases, the imaging biomarkers should be prioritised over molecular biomarkers in planning treatment because the latter fail to predict the severity of the disease. In combination with the use of the large section histopathology technique, imaging biomarkers help alleviate some of the current problems in breast cancer management, such as over- and under-assessment of disease extent, which carry the risk of overtreatment and undertreatment.

Exonic mutations in cell-cell adhesion may contribute to CADASIL-related CSVD pathology.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a condition caused by mutations in NOTCH3 and results in a phenotype characterised by recurrent strokes, vascular dementia and migraines. Whilst a genetic basis for the disease is known, the molecular mechanisms underpinning the pathology of CADASIL are still yet to be determined. Studies conducted at the Genomics Research Centre (GRC) have also identified that only 15-23% of individuals clinically suspected of CADASIL have mutations in NOTCH3. Based on this, whole exome sequencing was used to identify novel genetic variants for CADASIL-like cerebral small-vessel disease (CSVD). Analysis of functionally important variants in 50 individuals was investigated using overrepresentation tests in Gene ontology software to identify biological processes that are potentially affected in this group of patients. Further investigation of the genes in these processes was completed using the TRAPD software to identify if there is an increased number (burden) of mutations that are associated with CADASIL-like pathology. Results from this study identified that cell-cell adhesion genes were positively overrepresented in the PANTHER GO-slim database. TRAPD burden testing identified n = 15 genes that had a higher number of rare (MAF < 0.001) and predicted functionally relevant (SIFT < 0.05, PolyPhen > 0.8) mutations compared to the gnomAD v2.1.1 exome control dataset. Furthermore, these results identified ARVCF, GPR17, PTPRS, and CELSR1 as novel candidate genes in CADASIL-related pathology. This study identified a novel process that may be playing a role in the vascular damage related to CADASIL-related CSVD and implicated n = 15 genes in playing a role in the disease.

Updated Review of Major Cancer Risk Factors and Screening Test use in the United States, with a Focus on Changes During the COVID-19 Pandemic.

We present national and state representative prevalence estimates of modifiable cancer risk factors, preventive behaviors and services, and screening, with a focus on changes during the COVID-19 pandemic. Between 2019 and 2021, current smoking, physical inactivity, and heavy alcohol consumption declined, and human papillomavirus vaccination and stool testing for colorectal cancer screening uptake increased. In contrast, obesity prevalence increased, while fruit consumption and cervical cancer screening declined during the same timeframe. Favorable and unfavorable trends were evident during the second year of the COVID-19 pandemic that must be monitored as more years of consistent data are collected. Yet disparities by racial/ethnic and socioeconomic status persisted, highlighting the continued need for interventions to address suboptimal levels among these population subgroups.