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Abstract Background Cervical cancer is the second most prominent cancer among women in Bangladesh, which is mainly caused by persistent infection with high-risk human papillomavirus (hrHPV). This study aims to evaluate impact of hrHPV prevalence on cost-effectiveness of screening with self-sampling hrHPV testing versus visual inspection with acetic acid (VIA) for cervical cancer screening in low- and middle-income countries with Bangladesh as an example. Methods A micro-simulation Markov model was developed from a health system perspective in Bangladesh to evaluate the cost-effectiveness of screening with self-sampling hrHPV testing followed by VIA and VIA as primary screening method followed by colposcopy. We compared these strategies in optimal (70%) and realistic (8.7%) uptake scenarios, considering different hrHPV prevalence rates. Key indicators for cost-effectiveness were number of prevented cervical cancers cases and incremental cost-effectiveness ratio (ICER). Results The number of cervical cancers cases prevented by screening and cost-effectiveness of screening strategies increased as hrHPV prevalence increased. In both optimal and realistic uptake scenarios, hrHPV test + VIA strategy prevented more cancers than VIA + colposcopy strategy in most instances. Regardless of the uptake, both screening strategies were cost-effective compared to no screening within a hrHPV prevalence range of 2–30%, and the hrHPV test-based strategy was cost-effective compared with VIA-based strategy. When the price of hrHPV test was estimated 50% lower (10 USD), the hrHPV test-based strategy gained more life years at nearly the same cost as the VIA-based strategy. Conclusions Our study demonstrates that the hrHPV test + VIA strategy is cost-effective both compared to no screening and VIA + colposcopy screening strategy under the optimal (70%) and realistic (8.7%) uptake scenarios, with greater cost-effectiveness at higher hrHPV prevalence levels. While VIA-based strategy is cheaper, self-sampling hrHPV test-based strategy offers greater health benefits. Implementing hrHPV testing in national screening programs at lower hrHPV test prices is crucial for promoting health equity and accelerating cervical cancer elimination worldwide. In resource-constrained settings, screening with hrHPV testing should initially target high-prevalence populations.

Abstract Objective The aim of this study was to evaluate and compare reliability, costs, and radiation dose of dual-energy X-ray absorptiometry (DXA) to MRI and CT in measuring muscle mass for the diagnosis of sarcopenia. Methods Thirty-four consecutive DXA scans performed in surgically menopausal women from November 2019 until March 2020 were analyzed by two observers. Observers analyzed muscle mass of the lower limbs in every scan twice. Reliability was assessed by calculating inter- and intra-observer variability. Reliability from CT and MRI as well as radiation dose from CT and DXA were collected from literature. Costs for each type of scan were calculated according to the guidelines for economic evaluation of the Dutch National Health Care Institute. Results The 34 participants had a median age of 58 years (IQR 53–65) and a median body mass index of 24.6 (IQR 21.7–29.7). Inter-observer variability had an intraclass correlation coefficient (ICC) of 0.997 (95% CI 0.994–0.998) with a relative variability of 0.037 ± 0.022%. Regarding intra-observer variability, observer 1 had an ICC of 0.998 (95% CI 0.996–0.999) with a relative variability of 0.019 ± 0.016% and observer 2 had an ICC of 0.997 (95% CI 0.993–0.998) with a relative variability of 0.016 ± 0.011%. DXA costs were €62, CT €77, and MRI €195. The estimated radiation dose of CT was 2.5–3.0 mSv, for DXA this was 2–4 µSv. Conclusions DXA has lower costs and a lower radiation dose, with low inter- and intra-observer variability, compared to CT and MRI for assessing lower limb muscle mass. Trial registration Netherlands Trial Register; NL8068. Critical relevance statement DXA is a good alternative for CT and MRI in assessing lower limb muscle mass, with lower costs and lower radiation dose, while inter-observer and intra-observer variability are low. Key points • Screening for sarcopenia should be optimized as the population ages. • DXA outperformed CT and MRI in the measured metrics. • DXA validity should be further evaluated as an alternative to CT and MRI for sarcopenia evaluation. Graphical Abstract

Abstract Introduction Metformin and statins are considered as potential agents for prevention of breast cancer, however, existing evidence does not uniformly substantiate this claim, and the data is scarce concerning their interaction in relation to breast cancer risk. This study aims to investigate whether the effect of metformin on breast cancer incidence varied by statin use among women with type 2 diabetes mellitus (T2DM). Methods This study included women with T2DM, without a history of cancers, and followed up for more than one year from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) for the period 1998–2014. The dataset was structured using a person-time approach, where the cumulative medication usage was annually updated for each person. The extended Cox proportional hazards models were employed, reporting adjusted hazard ratios (HR) with 95% confidence intervals (CI). Results During a median follow-up of 5 years, 515 of 29,498 women received a breast cancer diagnosis. Each additional year of metformin or statins use corresponded to a decrease in breast cancer incidence, while the magnitude attenuated over time. Noteworthily, statin use modified the effect of metformin on breast cancer incidence. For instance, after 5 years of follow-up, one-year increase of metformin use among women who used statins for 3 years was linked to a substantially reduced breast cancer risk (HR, 95% CI: 0.88, 0.84–0.93), however, there was no significant decrease in risk for those non-statins users (HR, 95% CI: 0.96, 0.89–1.04). Conclusions Extending metformin or statin usage by one year conferred breast cancer protection in women with T2DM. Enhanced protective effect of metformin was observed among those who also use statins. These results suggest the potential of combined metformin and statin therapy as promising breast cancer prevention strategies.

Abstract Objective An increasing number of commercial deep learning computer-aided detection (DL-CAD) systems are available but their cost-saving potential is largely unknown. This study aimed to gain insight into appropriate pricing for DL-CAD in different reading modes to be cost-saving and to determine the potentially most cost-effective reading mode for lung cancer screening. Methods In three representative settings, DL-CAD was evaluated as a concurrent, pre-screening, and second reader. Scoping review was performed to estimate radiologist reading time with and without DL-CAD. Hourly cost of radiologist time was collected for the USA (€196), UK (€127), and Poland (€45), and monetary equivalence of saved time was calculated. The minimum number of screening CTs to reach break-even was calculated for one-time investment of €51,616 for DL-CAD. Results Mean reading time was 162 (95% CI: 111–212) seconds per case without DL-CAD, which decreased by 77 (95% CI: 47–107) and 104 (95% CI: 71–136) seconds for DL-CAD as concurrent and pre-screening reader, respectively, and increased by 33–41 s for DL-CAD as second reader. This translates into €1.0–4.3 per-case cost for concurrent reading and €0.8–5.7 for pre-screening reading in the USA, UK, and Poland. To achieve break-even with a one-time investment, the minimum number of CT scans was 12,300–53,600 for concurrent reader, and 9400–65,000 for pre-screening reader in the three countries. Conclusions Given current pricing, DL-CAD must be priced substantially below €6 in a pay-per-case setting or used in a high-workload environment to reach break-even in lung cancer screening. DL-CAD as pre-screening reader shows the largest potential to be cost-saving. Critical relevance statement Deep-learning computer-aided lung nodule detection (DL-CAD) software must be priced substantially below 6 euro in a pay-per-case setting or must be used in high-workload environments with one-time investment in order to achieve break-even. DL-CAD as a pre-screening reader has the greatest cost savings potential. Key points • DL-CAD must be substantially below €6 in a pay-per-case setting to reach break-even. • DL-CAD must be used in a high-workload screening environment to achieve break-even. • DL-CAD as a pre-screening reader shows the largest potential to be cost-saving. Graphical Abstract

Abstract Background Regular participation in cervical cancer screening is critical to reducing mortality. Although certain sociodemographic factors are known to be associated with one-time participation in screening, little is known about other factors that could be related to regular participation. Therefore, this study evaluated the association between health-related behavioral factors and regular participation in cervical cancer screening. Methods The Lifelines population-based cohort was linked to data for cervical cancer screening from the Dutch Nationwide Pathology Databank. We included women eligible for all four screening rounds between 2000 and 2019, classifying them as regular (4 attendances), irregular (1–3 attendances), and never participants. Multinomial logistic regression was performed to evaluate the association between behavioral factors and participation regularity, with adjustment made for sociodemographic factors. Results Of the 48,325 included women, 55.9%, 35.1%, and 9% were regular, irregular, and never screening participants. After adjustment for sociodemographic factors, the likelihood of irregular or never screening participation was increased by smoking, obesity, marginal or inadequate sleep duration, alcohol consumption and low physical activity, while it was decreased by hormonal contraception use. Conclusion An association exists between unhealthy behavioral factors and never or irregular participation in cervical cancer screening.

Objective: Assumptions on the natural history of ductal carcinoma in situ (DCIS) are necessary to accurately model it and estimate overdiagnosis. To improve current estimates of overdiagnosis (0–91%), the purpose of this review was to identify and analyse assumptions made in modelling studies on the natural history of DCIS in women.Methods: A systematic review of English full-text articles using PubMed, Embase, and Web of Science was conducted up to February 6, 2023. Eligibility and all assessments were done independently by two reviewers. Risk of bias and quality assessments were performed. Discrepancies were resolved by consensus. Reader agreement was quantified with Cohen's kappa. Data extraction was performed with three forms on study characteristics, model assessment, and tumour progression. Results: Thirty models were distinguished. The most important assumptions regarding the natural history of DCIS were addition of non-progressive DCIS of 20–100%, classification of DCIS into three grades, where high grade DCIS had an increased chance of progression to invasive breast cancer (IBC), and regression possibilities of 1–4%, depending on age and grade. Other identified risk factors of progression of DCIS to IBC were younger age, birth cohort, larger tumour size, and individual risk. Conclusion: To accurately model the natural history of DCIS, aspects to consider are DCIS grades, non-progressive DCIS (9–80%), regression from DCIS to no cancer (below 10%), and use of well-established risk factors for progression probabilities (age). Improved knowledge on key factors to consider when studying DCIS can improve estimates of overdiagnosis and optimization of screening.

Objective: To identify the differences between early- (EOCRC) and late-onset colorectal cancer (LOCRC), and to evaluate the determinants of one-year all-cause mortality among advanced-stage patients. Methods: A retrospective cohort study was carried out. CRC patients ≥ 18 years old were included. Chi-Square test was applied to compare both groups. Uni- and multivariate regressions were performed to evaluate the determinants of one-year all-cause mortality in all advanced-stage patients regardless of age of onset. Results: A total of 416 patients were enrolled; 53.1 % were female. Ninety cases (21.6 %) had EOCRC and 326 (78.4 %) had LOCRC. EOCRC cases were predominantly sporadic (88.9 %). Histology of carcinoma other than adenocarcinoma (p = 0.044) and rectum tumors (p = 0.039) were more prevalent in EOCRC. LOCRC patients were more likely to have smoking history (p < 0.001) and right colon tumors (p = 0.039). Alcohol consumption history (odds ratio [OR]: 3.375, 95 %CI: 1.022–11.150) and stage IV (OR: 12.632, 95 %CI: 3.506–45.513) were associated with higher one-year all-cause mortality among advanced-stage patients, the opposite was noted with left colon tumors (OR: 0.045, 95 %CI: 0.003–0.588). Conclusion: EOCRC was predominantly sporadic and had more cases of uncommon histological subtypes and rectal tumors. LOCRC was characterized by a higher prevalence of smoking history. Multivariate regression revealed an association between higher one-year all-cause mortality and alcohol consumption history and stage IV in advanced-stage patients. CRC exhibited differences based on age of onset. The evaluated factors associated with CRC mortality provide valuable insights for healthcare professionals, emphasizing the importance of adequate clinical assessment and early CRC diagnosis.

Abstract Introduction Geriatric assessment (GA) is widely used to detect vulnerability in older patients. As this process is time-consuming, prescreening tools have been developed to identify patients at risk for frailty. We aimed to assess whether the Geriatric 8 (G8) or the Korean Cancer Study Group Geriatric Score (KG-7) shows better performance in identifying patients who are in need of full GA. Materials and methods A consecutive series of patients aged ≥ 60 years with colorectal cancer were included. The sensitivity, specificity, predictive value, and 95% confidence intervals (95% CI) were calculated for the G8 and the KG-7 using the results of GA as the reference standard. ROC(Receiver Operating Characteristic) was used to evaluate the accuracy of the G8 and the KG-7. Results One hundred four patients were enrolled. A total of 40.4% of patients were frail according to GA, and 42.3% and 50.0% of patients were frail based on the G8 and the KG-7, respectively. The sensitivity and specificity of the G8 were 90.5% (95% CI: 77.4–97.3%) and 90.3% (95% CI: 80.1–96.4%), respectively. For the KG-7, the sensitivity and specificity were 83.3% (95% CI: 68.6–93.0%) and 72.6% (95% CI: 59.8–83.1%), respectively. Compared to the KG-7, the G8 had a higher predictive accuracy (AUC: (95% CI): 0.90 (0.83–0.95) vs. 0.78 (0.69–0.85); p

BackgroundDuring the COVID-19 pandemic, many healthcare workers faced extreme working conditions and were at higher risk of infection with the coronavirus. These circumstances may have led to mental health problems, such as anxiety, among healthcare workers. Most studies that examined anxiety among healthcare workers during the COVID-19 pandemic were cross-sectional and focused on the first months of the pandemic only. Therefore, this study aimed to investigate the longitudinal association between working in healthcare and anxiety during a long-term period (i.e., 18 months) of the COVID-19 pandemic.MethodsData were used from online questionnaires of the Lifelines COVID-19 prospective cohort with 22 included time-points (March 2020–November 2021). In total, 2,750 healthcare workers and 9,335 non-healthcare workers were included. Anxiety was assessed with questions from the Mini-International Neuropsychiatric Interview, and an anxiety sum score (0–7) was calculated. Negative binomial generalized estimating equations (GEE), adjusted for demographic, work and health covariates, were used to examine the association between working in healthcare and anxiety.ResultsAnxiety sum scores over time during the COVID-19 pandemic were similar for healthcare workers and non-healthcare workers. No differences between the anxiety sum scores of healthcare workers and non-healthcare workers were found [incidence rate ratio (IRR) = 0.97, 95% CI = 0.91–1.04].ConclusionThis study did not find differences between healthcare workers and non-healthcare in perceived anxiety during the COVID-19 pandemic.

Abstract Background Physical performance tests are a reflection of health in older adults. The Timed Up and Go test is an easy-to-administer tool measuring physical performance. In older adults undergoing oncologic surgery, an impaired TUG has been associated with higher rates of postoperative complications and increased short term mortality. The objective of this study is to investigate the association between physical performance and long term outcomes. Methods Patients aged ≥65 years undergoing surgery for solid tumors in three prospective cohort studies, ‘PICNIC’, ‘PICNIC B-HAPPY’ and ‘PREOP’, were included. The TUG was administered 2 weeks before surgery, a score of ≥12 seconds was considered to be impaired. Primary endpoint was 5-year survival, secondary endpoint was 30-day major complications. Survival proportions were estimated using Kaplan-Meier curves. Cox- and logistic regression analysis were used for survival and complications respectively. Hazard ratios (aHRs) and Odds ratios (aOR) were adjusted for literature-based and clinically relevant variables, and 95% confidence intervals (95% CIs) were estimated using multivariable models. Results In total, 528 patients were included into analysis. Mean age was 75 years (SD 5.98), in 123 (23.3%) patients, the TUG was impaired. Five-year survival proportions were 0.56 and 0.49 for patients with normal TUG and impaired TUG respectively. An impaired TUG was an independent predictor of increased 5-year mortality (aHR 1.43, 95% CI 1.02-2.02). The TUG was not a significant predictor of 30-day major complications (aOR 1.46, 95% CI 0.70-3.06). Conclusions An impaired TUG is associated with increased 5-year mortality in older adults undergoing surgery for solid tumors. It requires further investigation whether an impaired TUG can be reversed and thus improve long-term outcomes. Trial registration The PICNIC studies are registered in the Dutch Clinical Trial database at www.trialregister.nl: NL4219 (2010-07-22) and NL4441 (2014-06-01). The PREOP study was registered with the Dutch trial registry at www.trialregister.nl: NL1497 (2008-11-28) and in the United Kingdom register (Research Ethics Committee reference 10/H1008/59). https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/?page=15&query=preop&date_from=&date_to=&research_type=&rec_opinion=&relevance=true .

Abstract Background Due to identifiability problems, statistical inference about treatment-by-period interactions has not been discussed for stepped wedge designs in the literature thus far. Unidirectional switch designs (USDs) generalize the stepped wedge designs and allow for estimation and testing of treatment-by-period interaction in its many flexible design forms. Methods Under different forms of the USDs, we simulated binary data at both aggregated and individual levels and studied the performances of the generalized linear mixed model (GLMM) and the marginal model with generalized estimation equations (GEE) for estimating and testing treatment-by-period interactions. Results The parallel group design had the highest power for detecting the treatment-by-period interactions. While there was no substantial difference between aggregated-level and individual-level analysis, the GLMM had better point estimates than the marginal model with GEE. Furthermore, the optimal USD for estimating the average treatment effect was not efficient for treatment-by-period interaction and the marginal model with GEE required a substantial number of clusters to yield unbiased estimates of the interaction parameters when the correlation structure is autoregressive of order 1 (AR1). On the other hand, marginal model with GEE had better coverages than GLMM under the AR1 correlation structure. Conclusion From the designs and methods evaluated, in general, parallel group design with a GLMM is, preferred for estimation and testing of treatment-by-period interaction in a clustered randomized controlled trial for a binary outcome.

Background To decrease the burden of breast cancer (BC), the Chinese government recently introduced biennial mammography screening for women aged 45-70 years. In this study, we assess the effectiveness and cost-effectiveness of implementing this programme in urban China using a micro-simulation model.Methods The ‘Simulation Model on radiation Risk and breast cancer Screening’ (SiMRiSc) was applied, with parameters updated based on available data for the Chinese population. The base scenario was biennial mammography screening for women aged 45-70 years, and this was compared to a reference population with no screening. Seven alternative scenarios were then simulated by varying the screening intervals and participant ages. This analysis was conducted from a societal perspective. The discounted incremental cost- effectiveness ratio (ICER) was compared to a threshold of triple the gross domestic product (GDP) per life years gained (LYG), which was 30 785 USD/LYG. Univariate sensitivity analyses were conducted to evaluate model robustness. In addition, a budget impact analysis was performed by comparing biennial screening with no screening at a time horizon of 10 years.Results Compared with no screening, the base scenario was cost-effective in urban China, giving a discounted average cost-effectiveness ratio (ACER) of 17 309 USD/LYG. The model was most sensitive to the cost of mammography per screen, followed by mean size of self- detected tumours, mammographic breast density and the cumulative lifetime risk of BC. The efficient frontier showed that at a threshold of 30 785 USD/LYG, the base scenario was the optimal scenario with a discounted ICER of 25 261 USD/LYG. Over 10 years, screening would incur a net cost of almost 38.1 million USD for a city with 1 million citizens. Conclusion Compared to no screening, biennial mammography screening for women aged from 45-70 is cost-effective in urban China.

Abstract Background High-risk human papillomavirus (hrHPV) testing has been recommended by the World Health Organization as the primary screening test in cervical screening programs. The option of self-sampling for this screening method can potentially increase women’s participation. Designing screening programs to implement this method among underscreened populations will require contextualized evidence. Methods PREvention and SCReening Innovation Project Toward Elimination of Cervical Cancer (PRESCRIP-TEC) will use a multi-method approach to investigate the feasibility of implementing a cervical cancer screening strategy with hrHPV self-testing as the primary screening test in Bangladesh, India, Slovak Republic and Uganda. The primary outcomes of study include uptake and coverage of the screening program and adherence to follow-up. These outcomes will be evaluated through a pre-post quasi-experimental study design. Secondary objectives of the study include the analysis of client-related factors and health system factors related to cervical cancer screening, a validation study of an artificial intelligence decision support system and an economic evaluation of the screening strategy. Discussion PRESCRIP-TEC aims to provide evidence regarding hrHPV self-testing and the World Health Organization’s recommendations for cervical cancer screening in a variety of settings, targeting vulnerable groups. The main quantitative findings of the project related to the impact on uptake and coverage of screening will be complemented by qualitative analyses of various determinants of successful implementation of screening. The study will also provide decision-makers with insights into economic aspects of implementing hrHPV self-testing, as well as evaluate the feasibility of using artificial intelligence for task-shifting in visual inspection with acetic acid. Trial registration ClinicalTrials.gov, NCT05234112 . Registered 10 February 2022

Research has long since confirmed the benefits of regular cervical cancer screening (CCS) worldwide. However, some developed countries have low participation rates despite well-organized screening programs. Given that studies in Europe typically define participation in 12-month windows from an invitation, we evaluated both whether extending this defined time window could reveal the true participation rate and how sociodemographic determinants affect participation delays. This involved linking data from the Lifelines population-based cohort with CCS-related data from the Dutch Nationwide Pathology Databank and including data for 69 185 women eligible for screening in the Dutch CCS program between 2014 and 2018. We then estimated and compared the participation rates for 15- and 36-month time windows and categorized women by the primary screening window into timely participation (within 15 months) and delayed participation (within 15–36 months) groups, before performing multivariable logistic regression to evaluate the association between delayed participation and the sociodemographic determinants. Participation rates for the 15- and 36-month windows were 71.1% and 77.0%, respectively, with participation considered timely in 49 224 cases and delayed in 4047 cases. Delayed participation was associated with age 30–35 years (odds ratio [OR]: 2.88, 95 %CI: 2.67–3.11), higher education (OR: 1.50, 95 %CI: 1.35–1.67), the high-risk human papillomavirus test-based program (OR: 1.67, 95 %CI: 1.56–1.79), and pregnancy (OR: 4.61, 95 %CI: 3.88–5.48). These findings show that a 36-month window for monitoring attendance at CCS better reflects the actual participation rate by accommodating possible delayed uptake among younger, pregnant, and highly educated women.

Photosensitizing properties of hydrochlorothiazide may increase skin cancer risk. To date, study findings on the association between hydrochlorothiazide use and skin cancer risk are inconsistent, notably regarding confounding and dose-response. The aim of this study was to investigate the association between hydrochlorothiazide use and incidence of skin cancer in a cohort of unselected Caucasian adults, taking dosing into account. As part of the PharmLines Initiative, which links data from the Lifelines Cohort Study and prescription database IADB.nl, patients aged ≥ 40 years were included from Lifelines, a prospective population-based cohort study in the north of the Netherlands. Skin cancer incidence was compared between subjects starting hydrochlorothiazide treatment (n = 608), subjects starting treatment with other antihypertensives (n = 508), and non-antihypertensive long-term medication users (n = 1,710). Cox regression analyses were performed to obtain hazard ratios, adjusted for potential confounders. The risk of any skin cancer, keratinocyte carcinoma, basal cell carcinoma and squamous cell carcinoma was not significantly increased in general hydrochlorothiazide users. A clear association was observed between high cumulative hydrochlorothiazide use (≥ 5,000 defined daily dose; ≥ 125,000 mg) and the risk of any skin cancer (adjusted hazard ratio 5.32, 95% confidence interval (95% CI) 2.40–11.81), keratinocyte carcinoma (adjusted hazard ratio 7.31, 95% CI 3.12–17.13), basal cell carcinoma (adjusted hazard ratio 7.72, 95% CI 3.11–19.16) and squamous cell carcinoma (adjusted hazard ratio 19.63, 95% CI 3.12–123.56). These findings should lead to awareness with high use of hydrochlorothiazide in Caucasian adults.

Background: The effectiveness of lung cancer screening with low-dose computed tomography (LDCT) has been established. The current study evaluates the cost-effectiveness of lung cancer screening with LDCT in a general population in China. Methods: A previously validated micro-simulation model was used to simulate a cohort of men and women on a lifetime horizon in the presence and absence of LDCT screening. The modeling data were collected from numerous national and international sources. Simulated screening scenarios included different combinations of screening intervals and start and stop ages. Additional costs (valued in Chinese Yuan, CNY; 1 USD = 6.8976 CNY, 1 EUR = 7.8755 CNY in 2020), life-years gained (LYG) and mortality reduction due to screening were also determined. The costs and life-years were discounted by 3%. All results were scaled to 1,000 individuals. The average cost-effectiveness ratio (ACER) was calculated. A willingness-to-pay threshold of CNY 217.3k / LYG was considered. A healthcare system perspective was adopted. Results: Compared to no screening, lung cancer screening by LDCT in a general Chinese population yielded 21.0 – 36.7 LYG in men and 9.2 – 16.6 LYG in women across the scenarios. For men, biennial LDCT screening yielded an ACER of CNY 171.4k – 306.3k / LYG relative to no screening. Biennial screening performed between 55 and 75 years of age was optimal at the defined threshold; it resulted in CNY 174.6k / LYG and a lung cancer mortality reduction of 9.1%, and this scenario had a 75% probability of being cost-effective. For women, the ACER ranged from CNY 364.2k to 1193.3k / LYG. Conclusions: In China, lung cancer screening with LDCT in the general population including never smokers could be cost-effective for men with 75% probability, but not for women. The optimal strategy for men would be performing biennial screening between 55 and 75 years of age.

Introduction: Magnetic resonance imaging (MRI) has shown the potential to improve the screening effectiveness among women with dense breasts. The introduction of fast abbreviated protocols (AP) makes MRI more feasible to be used in a general population. We aimed to investigate the cost-effectiveness of AP-MRI in women with dense breasts (heterogeneously/extremely dense) in a population-based screening program. Methods: A previously validated model (SiMRiSc) was applied, with parameters updated for women with dense breasts. Breast density was assumed to decrease with increased age. The base scenarios included six biennial AP-MRI strategies, with biennial mammography from age 50–74 as reference. Fourteen alternative scenarios were performed by varying screening interval (triennial and quadrennial) and by applying a combined strategy of mammography and AP-MRI. A 3% discount rate for both costs and life years gained (LYG) was applied. Model robustness was evaluated using univariate and probabilistic sensitivity analyses. Results: The six biennial AP-MRI strategies ranged from 132 to 562 LYG per 10,000 women, where more frequent application of AP-MRI was related to higher LYG. The optimal strategy was biennial AP-MRI screening from age 50–65 for only women with extremely dense breasts, producing an incremental cost-effectiveness ratio of € 18,201/LYG. At a threshold of € 20,000/LYG, the probability that the optimal strategy was cost-effective was 79%. Conclusion: Population-based biennial breast cancer screening with AP-MRI from age 50–65 for women with extremely dense breasts might be a cost-effective alternative to mammography, but is not an option for women with heterogeneously dense breasts.

Summary: Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning and thresholding (P + T) and PRS-continuous shrinkage (CS). For both methods, using a European-based linkage disequilibrium (LD) reference panel resulted in comparable or higher prediction accuracy compared with several other non-European-based panels. PRS-CS overall outperformed the classic P + T method, especially for endpoints with higher SNP-based heritability. Notably, prediction accuracy is heterogeneous across endpoints, biobanks, and ancestries, especially for asthma, which has known variation in disease prevalence across populations. Overall, we provide lessons for PRS construction, evaluation, and interpretation using GBMI resources and highlight the importance of best practices for PRS in the biobank-scale genomics era.

The aim of this phantom study was to assess the detectability and volumetric accuracy of pulmonary nodules on photon-counting detector CT (PCD-CT) at different low-dose levels compared to conventional energy-integrating detector CT (EID-CT). In-house fabricated artificial nodules of different shapes (spherical, lobulated, spiculated), sizes (2.5–10 mm and 5–1222 mm3), and densities (−330 HU and 100 HU) were randomly inserted into an anthropomorphic thorax phantom. The phantom was scanned with a low-dose chest protocol with PCD-CT and EID-CT, in which the dose with PCD-CT was lowered from 100% to 10% with respect to the EID-CT reference dose. Two blinded observers independently assessed the CT examinations of the nodules. A third observer measured the nodule volumes using commercial software. The influence of the scanner type, dose, observer, physical nodule volume, shape, and density on the detectability and volumetric accuracy was assessed by a multivariable regression analysis. In 120 CT examinations, 642 nodules were present. Observer 1 and 2 detected 367 (57%) and 289 nodules (45%), respectively. With PCD-CT and EID-CT, the nodule detectability was similar. The physical nodule volumes were underestimated by 20% (range 8–52%) with PCD-CT and 24% (range 9–52%) with EID-CT. With PCD-CT, no significant decrease in the detectability and volumetric accuracy was found at dose reductions down to 10% of the reference dose (p > 0.05). The detectability and volumetric accuracy were significantly influenced by the observer, nodule volume, and a spiculated nodule shape (p < 0.05), but not by dose, CT scanner type, and nodule density (p > 0.05). Low-dose PCD-CT demonstrates potential to detect and assess the volumes of pulmonary nodules, even with a radiation dose reduction of up to 90%.

Zhang et al. develop a natural language processing approach, based on the BERT model, to extract linguistic information from chest X-ray radiography reports. The authors establish a 25-label classification system for abnormal findings described in the reports and validate their model using data from multiple sites.

IntroductionWorking from home during the COVID-19 pandemic has been associated both with physical inactivity and musculoskeletal pain. However, it has not been examined whether physical activity and sedentary behavior are underlying mechanisms in the association between working from home and musculoskeletal pain. Therefore, we examined their mediating role in this association.MethodsData were used from 24 questionnaire rounds of the Lifelines COVID-19 cohort (March 2020–January 2022). Longitudinal information on work situation (location, home, hybrid), physical activity, sedentary behavior, and musculoskeletal pain was collected among 28,586 workers. Analysis of physical activity/sedentary behavior as mediators of the association between working from home and musculoskeletal pain was performed using multilevel structural equation modeling.ResultsHome workers more often had pain in the upper back [odds ratio (OR) = 1.17, 95%-confidence interval (CI) = 1.02–1.34] and arm, neck, and/or shoulder (ANS) (OR = 1.32, 95%-CI = 1.19–1.47) than location workers. Furthermore, home workers were more often sedentary for >9 h per work day than location workers (OR = 2.82, 95%-CI = 2.56–3.09), and being more sedentary was associated with musculoskeletal pain (upper back: OR = 1.17, 95%-CI = 1.06–1.30; ANS: OR = 1.25, 95%-CI = 1.16–1.34). Corresponding indirect effects were OR = 1.18 (95%-CI = 1.04–1.33) and OR = 1.26 (95%-CI = 1.12–1.35). No indirect effect was found for physical activity. Similar indirect effects were observed for hybrid workers.ConclusionHome and hybrid workers were more likely to have pain in the upper musculoskeletal system during the COVID-19 pandemic than location workers, which was partly mediated by increased sedentary behavior, but not by reduced physical activity. Measures to reduce sedentary time in home workers may contribute to preventing musculoskeletal pain.

Abstract Assessment of image noise is a relevant issue in computed tomography (CT). Noise is routinely measured by the standard deviation of density values (Hounsfield units, HU) within a circular region of interest (ROI). We explored the effect of a spherical volume of interest (VOI) on noise measurements. Forty-nine chronic obstructive pulmonary disease patients underwent CT with clinical protocol (regular dose [RD], volumetric CT dose index [CTDIvol] 3.04 mGy, 64-slice unit), and ultra-low dose (ULD) protocol (median CTDIvol 0.38 mGy, dual-source unit). Noise was measured in 27 1-cm2 ROIs and 27 0.75-cm3 VOIs inside the trachea. Median true noise was 21 HU (range 17-29) for RD-CT and 33 HU (26-39) for ULD-CT. The VOI approach resulted in a lower mean distance between limits of agreement compared to ROI: 5.9 versus 10.0 HU for RD-CT (−40%); 4.7 versus 9.9 HU for ULD-CT (−53%). Mean systematic bias barely changed: −1.6 versus −0.9HU for RD-CT; 0.0 to 0.4HU for ULD-CT. The average measurement time was 6.8 s (ROI) versus 9.7 (VOI), independent of dose level. For chest CT, measuring noise with a VOI-based instead of a ROI-based approach reduces variability by 40-53%, without a relevant effect on systematic bias and measurement time.

Abstract We investigated whether presence and characteristics of lung nodules in the general population using low-dose computed tomography (LDCT) varied by season. Imaging in Lifelines (ImaLife) study participants who underwent chest LDCT-scanning between October 2018 and October 2019 were included in this sub-study. Hay fever season (summer) was defined as 1st April to 30th September and Influenza season (winter) as 1st October to 31st March. All lung nodules with volume of ≥ 30 mm3 (approximately 3 mm in diameter) were registered. In total, 2496 lung nodules were found in 1312 (38%) of the 3456 included participants (nodules per participant ranging from 1 to 21, median 1). In summer, 711 (54%) participants had 1 or more lung nodule(s) compared to 601 (46%) participants in winter (p = 0.002). Of the spherical, perifissural and left-upper-lobe nodules, relatively more were detected in winter, whereas of the polygonal-, irregular-shaped and centrally-calcified nodules, relatively more were detected in summer. Various seasonal diseases with inflammation as underlying pathophysiology may influence presence and characteristics of lung nodules. Further investigation into underlying pathophysiology using short-term LDCT follow-up could help optimize the management strategy for CT-detected lung nodules in clinical practice.

Background: Instead of a single value for mammographic sensitivity, a sensitivity function based on tumor size more realistically reflects mammography’s detection capability. Because previous models may have overestimated size-specific sensitivity, we aimed to provide a novel approach to improve sensitivity estimation as a function of tumor size. Methods: Using aggregated data on interval and screen-detected cancers, observed tumor sizes were back-calculated to the time of screening using an exponential tumor growth model and a follow-up time of 4 years. From the observed number of detected cancers and an estimation of the number of false-negative cancers, a model for the sensitivity as a function of tumor size was determined. A univariate sensitivity analysis was conducted by varying follow-up time and tumor volume doubling time (TVDT). A systematic review was conducted for external validation of the sensitivity model. Results: Aggregated data of 22,915 screen-detected and 10,670 interval breast cancers from the Dutch screening program were used. The model showed that sensitivity increased from 0 to 85% for tumor sizes from 2 to 20 mm. When TVDT was set at the upper and lower limits of the confidence interval, sensitivity for a 20-mm tumor was 74% and 93%, respectively. The estimated sensitivity gave comparable estimates to those from two of three studies identified by our systematic review. Conclusion: Derived from aggregated breast screening outcomes data, our model’s estimation of sensitivity as a function of tumor size may provide a better representation of data observed in screening programs than other models.

Abstract Background There is wide variation in clinical practice for the early detection of prostate cancer, not least because of the ongoing debate about the benefits of prostate-specific antigen (PSA) testing. In this study, we aimed to assess the approaches, attitudes, and knowledge of general practitioners (GPs) regarding PSA testing in primary care in the Netherlands, particularly regarding recommendations for prostate cancer. Methods Questionnaire surveys were sent to 179 GPs in the north-east of the Netherlands, of which 65 (36%) were completed and returned. We also surveyed 23 GPs attending a postgraduate train-the-trainer day (100%). In addition to demographic data and practice characteristics, the 31-item questionnaire covered the attitudes, clinical practice, adherence to PSA screening recommendations, and knowledge concerning the recommendations for prostate cancer early detection. Statistical analysis was limited to the descriptive level. Results Most GPs (95%; n = 82) stated that they had at least read the Dutch GP guideline, but just half (50%; n = 43) also stated that they knew the content. Almost half (46%; n = 39) stated they would offer detailed counseling before ordering a PSA test to an asymptomatic man requesting a test. Overall, prostate cancer screening was reported to be of minor importance compared to other types of cancer screening. Conclusions Clinical PSA testing in primary care in this region of the Netherlands seems generally to be consistent with the relevant guideline for Dutch GPs that is restrictive to PSA testing. The next step will be to further evaluate the effects of the several PSA testing strategies.

BackgroundBreast cancer (BC) screening can be performed in a screening program (BCSP) or in opportunistic screening. The existing reviews on the determinants of non-participation depend on self-reported data which may be biased. Furthermore, no distinction was made between the probably different determinants of both screening strategies.ObjectiveTo find the determinants of non-participation in BCSP by means of a meta-analysis.MethodsPubMed, Embase, and Web of Science were searched for observational studies which quantified factors associated with non-participation in BCSP in a general population. Studies on opportunistic screening and studies using self-reported data were excluded. A random-effect model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Potential sources of heterogeneity were explored by stratification of the results.ResultsTwenty-nine studies with in a total of 20,361,756 women were included. Low income (OR: 1.20, 95% CI: 1.10–1.30), low education (OR: 1.18, 95% CI: 1.05–1.32), living far from an assigned screening unit (OR: 1.15, 95% CI: 1.07–1.24), being immigrant (OR: 2.64, 95% CI: 2.48–2.82), and having a male family doctor (OR: 1.43, 95% CI: 1.20–1.61) was associated with higher non-participation in screening. Reminders sent to non-attenders and estimations of ORs (adjusted or not) partly explained substantial heterogeneity.ConclusionIn this meta-analysis excluding studies on the non-participation in opportunistic screening, or with self-reported data on non-participation, the well-known determinants for non-participation are still significant, but less strong. This analysis only supports the relevance of meta-analysis of studies with registered non-participation in a BCSP.Systematic Review RegistrationPROSPERO, CRD42020154016.

Background:. Little is known about how satisfied women are with their breasts and which factors influence breast satisfaction. Therefore, the aim of this study was to elucidate this by collecting data on breast satisfaction from the general population in relation to age, body mass index, lifestyle, psychological, and physical well-being. Method:. This study was a cross-sectional population survey performed in 2019 in the north of the Netherlands, among randomly selected women between 20 and 80 years. Breast satisfaction was measured in the 1334 participants with the preoperative reconstruction BREAST-Q module. Other applied questionnaires were the Hospital Anxiety and Depression Scale, Short Form Survey (SF-36), and a custom-made questionnaire on lifestyle and baseline characteristics. Representativeness was assessed by comparing the participants with Dutch normative data. Possible factors influencing “satisfaction with breasts” were analyzed using multivariate linear regression analyses. Results:. The median (IQR) BREAST-Q score for “satisfaction with breasts” was mediocre: 63 (58–79) on a 0–100 scale. Higher age and higher SF-36 scores had a positive effect on breast satisfaction (P < 0.001 and P < 0.001, respectively) and a higher body mass index, smoking and anxiety score greater than 8 were negatively associated (P < 0.001, P = 0.013 and P < 0.001 respectively, multivariate linear regression analyses). Conclusion:. These data are the first European normative data and can serve as a reference in future population and patient-based studies regarding breast satisfaction.

Abstract Background Breast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer. The tumor microenvironment of male breast cancer is less well understood, and insight may improve male breast cancer management. The hepatocyte growth factor (HGF)/c-MET axis and the stromal cell-derived factor-1 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis are prognostic in women with breast cancer. We aimed to investigate these factors in male breast cancer and correlate them with patient survival. Methods From 841 Dutch males with breast cancer who were enrolled in the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program (NCT01101425) and diagnosed between 1990 and 2010, archival primary tumor samples were collected. Tissue microarrays were constructed with 3 cores per sample and used for immunohistochemical analysis of HGF, c-MET, CXCL12, and CXCR4. Overall survival (OS) of the patients without metastases (M0) was analyzed using the Kaplan-Meier method. The value of the markers regarding OS was determined using univariable and multivariable Cox regression analyses, providing hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results Of 720 out of 841 patients, sufficient tissue was available for analysis; 487 out of 720 patients had M0 disease. Patients with high HGF expression and high CXCL12 expression had a superior OS (low vs high expression of both markers, 7.5 vs 13.0 years, hazard ratio [HR] 0.64, 95% CI 0.49–0.84, P = 0.001 [HGF]; 9.1 vs 15.3 years, HR 0.63, 95% CI 0.45–0.87, P = 0.005 [CXCL12]). Multivariate analysis identified HGF as an independent predictor for OS (HR 0.64, 95% CI 0.47–0.88, P = 0.001). Conclusions HGF and CXCL12 tumor expression appear to identify male breast cancer patients with a relatively good prognosis. Possibly, this could support male breast cancer-specific management strategies in the future.

Abstract Background Endometrial sampling for the surveillance of women with Lynch syndrome is an invasive and painful procedure. The aim of this study was to evaluate the feasibility of a less invasive procedure of collecting vital cells by vaginal tampons. Methods This was a prospective feasibility study of women scheduled to undergo annual gynecological surveillance, including endometrial sampling. We included consecutive asymptomatic women with Lynch syndrome or first-degree relatives and asked them to insert a vaginal tampon 2–4 h before attending their outpatient appointment. Feasibility was evaluated by the following metrics: patient acceptance, pain intensity of each procedure (assessed by visual analog scale; range 0–10), and the presence of vital cells obtained by tampon-based or endometrial sampling methods. Two pathologists independently evaluated all samples. Results In total, 25 of 32 approached women completed the tampon-based procedure, with 23 of these subsequently undergoing invasive endometrial sampling. The median visual analog scale scores for tampon use and invasive endometrial sampling were 0 (range, 0–10) and 5.5 (range, 1–10) (p

Objectives: To evaluate the characteristics and work-up of small to intermediate-sized pulmonary nodules in a Chinese dedicated cancer hospital. Methods: Patients with pulmonary nodules 4–25 mm in diameter detected via computed tomography (CT) in 2013 were consecutively included. The analysis was restricted to patients with a histological nodule diagnosis or a 2-year follow-up period without nodule growth confirming benign disease. Patient information was collected from hospital records. Results: Among the 314 nodules examined in 299 patients, 212 (67.5%) nodules in 206 (68.9%) patients were malignant. Compared to benign nodules, malignant nodules were larger (18.0 mm vs. 12.5 mm, P < 0.001), more often partly solid (16.0% vs. 4.7%, P < 0.001) and more often spiculated (72.2% vs. 41.2%, P < 0.001), with higher density in contrast-enhanced CT (67.0 HU vs. 57.5 HU, P = 0.015). Final diagnosis was based on surgery in 232 out of 314 (73.9%) nodules, 166 of which were identified as malignant [30 (18.1%) stage III or IV] and 66 as benign. In 36 nodules (11.5%), diagnosis was confirmed by biopsy and the remainder verified based on stability of nodule size at follow-up imaging (n = 46, 14.6%). Among 65 nodules subjected to gene (EGFR) mutation analyses, 28 (43.1%) cases (EGFR19 n = 13; EGFR21 n = 15) were identified as EGFR mutant and 37 (56.9%) as EGFR wild-type. Prior to surgery, the majority of patients [n = 194 (83.6%)] received a contrast-enhanced CT scan for staging of both malignant [n = 140 (84.3%)] and benign [n = 54 (81.8%)] nodules. Usage of positron emission tomography (PET)-CT was relatively uncommon [n = 38 (16.4%)]. Conclusions: CT-derived nodule assessment assists in diagnosis of small to intermediate- sized malignant pulmonary nodules. Currently, contrast-enhanced CT is commonly used as the sole diagnostic confirmation technique for pre-surgical staging, often resulting in surgery for late-stage disease and unnecessary surgery in cases of benign nodules.

BackgroundTo establish a machine-learning-derived nomogram based on radiomic features and clinical factors to predict post-surgical 2-year progression-free survival (PFS) in patients with lung adenocarcinoma.MethodsPatients with >2 years post-surgical prognosis results of lung adenocarcinoma were included in Hospital-1 for model training (n = 100) and internal validation (n = 50), and in Hospital-2 for external testing (n = 50). A total of 1,672 radiomic features were extracted from 3D segmented CT images. The Rad-score was established using random survival forest by accumulating and weighting the top-20 imaging features contributive to PFS. A nomogram for predicting PFS was established, which comprised the Rad-score and clinical factors highly relevant to PFS.ResultsIn the training, internal validation, and external test groups, 69/100 (69%), 37/50 (74%) and 36/50 (72%) patients were progression-free at two years, respectively. According to the Rad-score, the integral of area under the curve (iAUC) for discriminating high and low risk of progression was 0.92 (95%CI: 0.77-1.0), 0.70 (0.41-0.98) and 0.90 (0.65-1.0), respectively. The C-index of Rad-score was 0.781 and 0.860 in the training and external test groups, higher than 0.707 and 0.606 for TNM stage, respectively. The nomogram integrating Rad-score and clinical factors (lung nodule type, cM stage and histological type) achieved a C-index of 0.845 and 0.837 to predict 2-year PFS, respectively, significantly higher than by only radiomic features (all p < 0.01).ConclusionThe nomogram comprising CT-derived radiomic features and risk factors showed a high performance in predicting post-surgical 2-year PFS of patients with lung adenocarcinoma, which may help personalize the treatment decisions.

BackgroundProstate cancer (PCa) is the most frequent cancer among men in Europe. Differences in PCa incidence around the world can be partly explained by variations in recommendations for prostate-specific antigen (PSA), particularly for early detection. For example, the PSA testing policy is more conservative in the Netherlands than in Germany. To better understand the relationship between PSA testing recommendations and PCa incidence, stage distribution, and mortality, we compared these variables over time between Lower Saxony in northwestern Germany and the neighboring province of Groningen in the Netherlands.MethodsPopulation data, tumor stage- and age group-specific PCa incidence (ICD-10 C61) and mortality rates for Lower Saxony and Groningen were obtained from the Lower Saxony Epidemiological Cancer Registry, the Netherlands Comprehensive Cancer Organization, and Statistics Netherlands for 2003–2012. Incidence and mortality rates per 100,000 person-years were age-standardized (ASR, old European standard). Trends in age-standardized incidence rates (ASIR) and mortality rates (ASMR) for specific age groups were assessed using joinpoint regression.ResultsThe mean annual PCa ASIR between 2003 and 2012 was on average 19.9% higher in Lower Saxony than in Groningen (120.5 vs. 100.5 per 100,000), while the mean annual ASMR was on average 24.3% lower in Lower Saxony than in Groningen (21.5 vs. 28.4 per 100,000). Between 2003 and 2012, the average annual percentage change (AAPC) in PCa incidence rates did not change significantly in either Lower Saxony (−1.8%, 95% CI −3.5, 0.0) or Groningen (0.2%, 95% CI −5.0, 5.7). In contrast, the AAPC in mortality rate decreased significantly during the same time period in Lower Saxony (−2.5%, 95% CI −3.0, −2.0) but not in Groningen (0.1%, 95% CI −2.4, 2.6).ConclusionsHigher PCa incidence and lower PCa-related mortality was detected in Lower Saxony than in Groningen. Although recommendations on PSA testing may play a role, the assessed data could not offer obvious explanations to the observed differences. Therefore, further investigations including data on the actual use of PSA testing, other influences (e.g., dietary and ethnic factors), and better data quality are needed to explain differences between the regions.

Background: In Flanders, breast cancer (BC) screening is performed in a population-based breast cancer screening program (BCSP), as well as in an opportunistic setting. Women with different socio-demographic characteristics are not equally covered by BC screening.Objective: To evaluate the role of socio-demographic characteristics on the lowest 10th and highest 90th quantile levels of BC screening coverage.Methods: The 2017 neighborhood-level coverage rates of 8,690 neighborhoods with women aged 50–69 and eligible for BCSP and opportunistic screening were linked to socio-demographic data. The association between socio-demographic characteristics and the coverage rates of BCSP and opportunistic screening was evaluated per quantile of coverage using multivariable quantile regression models, with specific attention to the lowest 10th and highest 90th quantiles.Results: The median coverage in the BCSP was 50%, 33.5% in the 10th quantile, and 64.5% in the 90th quantile. The median coverage of the opportunistic screening was 12, 4.2, and 24.8% in the 10th and 90th quantile, respectively. A lower coverage of BCSP was found in neighborhoods with more foreign residents and larger average household size, which were considered indicators for a lower socioeconomic status (SES). However, a higher average personal annual income, which was considered an indicator for a higher SES, was also found in neighborhoods with lower coverage of BCSP. For these neighborhoods, that have a relatively low and high SES, the negative association between the percentage of foreign residents, average household size, and average personal annual income and the coverage in the BCSP had the smallest regression coefficient and 95% confidence interval (CI) values were −0.75 (95% CI: −0.85, −0.65), −13.59 (95% CI: −15.81, −11.37), and −1.05 (95% CI: −1.18, −0.92), respectively, for the 10th quantile. The neighborhoods with higher coverage of opportunistic screening had a relatively higher average personal annual income, with the largest regression coefficient of 1.72 (95% CI: 1.59, 1.85) for the 90th quantile.Conclusions: Women from relatively low and high SES neighborhoods tend to participate less in the BCSP, whereas women with a relatively high SES tend to participate more in opportunistic screening. For women from low SES neighborhoods, tailored interventions are needed to improve the coverage of BCSP.

This supplementary data is supportive to the research article entitled ‘Cost-effectiveness of lung cancer screening with low-dose computed tomography (LDCT) in heavy smokers: A micro-simulation modelling study’ (Yihui Du et al. 2020). This supplementary contains a description of the model input and the related model output data that were not included in the research article. The input data used for the tumour growth model and the self-detected tumour size model are provided. The output data of this article include the data used for cost-effectiveness analysis of lung cancer LDCT screening with the Dutch and international discount rates, the data of the sensitivity analysis, and the data of the model validation.

Objective European lung cancer screening studies using computed tomography (CT) have shown that a management protocol based on measuring lung nodule volume and volume doubling time (VDT) is more specific for early lung cancer detection than a diameter-based protocol. However, whether this also applies to a Chinese population is unclear. The aim of this study is to compare the diagnostic performance of a volume-based protocol with a diameter-based protocol for lung cancer detection and optimize the nodule management criteria for a Chinese population.Methods This study has a population-based, prospective cohort design and includes 4000 participants from the Hexi district of Tianjin, China. Participants will undergo low-dose chest CT at baseline and after 1 year. Initially, detected lung nodules will be evaluated for diameter and managed according to a routine diameter-based protocol (Clinical Practice Guideline in Oncology for Lung Cancer Screening, Version 2.2018). Subsequently, lung nodules will be evaluated for volume and management will be simulated according to a volume-based protocol and VDT (a European lung nodule management protocol). Participants will be followed up for 4 years to evaluate lung cancer incidence and mortality. The primary outcome is the diagnostic performance of the European volume-based protocol compared to diameter-based management regarding lung nodules detected using low-dose CT.Results The diagnostic performance of volume- and diameter-based management for lung nodules in a Chinese population will be estimated and compared.Conclusions Through the study, we expect to improve the management of lung nodules and early detection of lung cancer in Chinese populations.

Abstract Background This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with mammographically dense breasts in screening and diagnosis. Methods Two independent reviewers identified screening or diagnostic studies reporting at least one of four outcomes (cancer detection rate-CDR, recall rate, sensitivity and specificity) for DBT and DM in women with mammographically dense breasts. Study quality was assessed using QUADAS-2. Meta-analysis of CDR and recall rate used a random effects model. Summary ROC curve summarized sensitivity and specificity. Results Sixteen studies were included (five diagnostic; eleven screening). In diagnosis, DBT increased sensitivity (84%–90%) versus DM alone (69%–86%) but not specificity. DBT improved CDR versus DM alone (RR: 1.16, 95% CI 1.02–1.31). In screening, DBT + DM increased CDR versus DM alone (RR: 1.33, 95% CI 1.20–1.47 for retrospective studies; RR: 1.52, 95% CI 1.08–2.11 for prospective studies). Recall rate was significantly reduced by DBT + DM in retrospective studies (RR: 0.72, 95% CI 0.64–0.80) but not in two prospective studies (RR: 1.12, 95% CI 0.76–1.63). Conclusion In women with mammographically dense breasts, DBT+/−DM increased CDR significantly (versus DM) in screening and diagnosis. In diagnosis, DBT+/−DM increased sensitivity but not specificity. The effect of DBT + DM on recall rate in screening dense breasts varied between studies.

Abstract Background Patients with type 2 diabetes (T2D) are at increased risk for developing cancer. As approximately 8% of the world’s population is living with T2D, even a slight increase in cancer risk could result in an enormous impact on the number of persons developing cancer. In addition, several glucose lowering drug classes for treating patients with T2D have been associated with a difference in risk of cancer overall, and especially for obesity related cancers. In what way and to what degree cancer risk is modified by the use of different sulfonylureas (SU) is unclear. The primary aim of this study will be to evaluate within-class SU differences in obesity related cancer risk. Secondary aims will be to investigate within-class SU differences in risk for all cancers combined and site-specific cancers separately (i.e. breast, colorectal, prostate, bladder and lung cancer) and to account for duration-response relationships between individual SU use and cancer risk. Methods Patients will be selected from a Dutch primary care cohort of patients with T2D linked with the Dutch Cancer Registration (ZODIAC-NCR). Within this cohort study annually collected clinical data (e.g. blood pressure, weight, HbA1c) and nationwide data on cancer incidence are available. Time-dependent cox proportional hazard analyses will be performed to evaluate SU cancer risk, adjusted for potential confounders. Discussion This study will be the first prospective cohort study investigating within-class SU differences in cancer risk and could contribute to improved decision making regarding the individual drugs within the class of SUs, and possibly improve quality of life and result in an increased cost-effectiveness of healthcare in patients with T2D. Trial registration Nederlands Trialregister ( NTR6166 ), 6 Jan 2017.

Background: An ongoing controversy exists on the role of folic acid supplementation in colorectal cancer risk among epidemiological studies. Objective: To assess the association between maternal folic acid supplementation and colorectal cancer risk. Methods: A paired matched case control study of 405 subjects was performed, including women residing in 135 villages of East Azerbaijan, Iran. Per area, subjects were followed regularly in local healthcare centers, where health- and social-related information have been collected prospectively in face to face interviews by well-trained health workers. We extracted folic acid supplement intake, baseline characteristics, and confounders from healthcare records. The data for study participants were linked to national cancer registry repositories, from which we retrieved the data of 135 women diagnosed with colorectal cancer between 2005 to 2015. Two hundred seventy controls were individually matched with cases in terms of residing village, age, and gender. We applied multivariate conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Findings: There was no significant association between folic acid supplementation and colorectal cancer risk in those with history of folic acid intake compared to those with no history of intake (OR 0.95; 95% CI 0.59 to 1.53), in those with less than five years of folic acid (0.79; 0.45 to 1.39) or in those with ≥5 years intake (1.09; 0.52 to 2.26). This risk did not change after adjustment for covariates or further stratification. Conclusions: Maternal folic acid supplementation did not affect colorectal cancer risk in a population where supplemental folic acid is prescribed with regular intervals for women of child-bearing age.

In Asian countries, ultrasound has been proposed as a possible alternative for mammography in breast cancer screening because of its superiority in dense breasts, accessibility and low costs. This research aimed to meta-analyze the evidence for the diagnostic performance of ultrasound compared to mammography for breast cancer screening in Asian women. PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched for studies that concurrently compared mammography and ultrasound in 2000–2019. Data extraction and risk of bias were performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) statement. The primary outcome was the sensitivity and specificity. Bivariate random models were used to generate pooled estimates of diagnostic parameters and 95% confidence intervals (95% CI). In total, 4424 studies were identified of which six studies met the inclusion criteria with a sample size of 124,425 women. The pooled mean prevalence of the included studies was 3.7‰ (range: 1.2–5.7‰). The pooled sensitivity of mammography was significantly higher than that of ultrasound (0.81 [95% CI 0.71–0.88] versus 0.65 [95% CI 0.58–0.72], p = 0.03), but no significant differences were found in specificity (0.98 [95% CI: 0.94–1.00] versus 0.99 [95% CI: 0.97–1.00], p = 0.65). In conclusion, based on the currently available data on sensitivity alone, there is no indication that ultrasound can replace mammography in breast cancer screening in Asian women.

The prognosis of epithelial ovarian cancer (EOC), the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a “universal” vaccine strategy. We determined the expression of tumor antigens in the context of MHC class I expression in 270 primary tumor samples using tissue microarray. Expression of tumor antigens p53, SP17, survivin, WT1, and NY-ESO-1 was observed in 120 (48.0%), 173 (68.9%), 208 (90.0%), 129 (56.3%), and 27 (11.0%) of 270 tumor specimens, respectively. In 93.2% of EOC, at least one of the investigated tumor antigens was (over)expressed. Expression of MHC class I was observed in 78.1% of EOC. In 3 out 4 primary tumors, (over)expression of a tumor antigen combined with MHC class I was observed. These results indicate that a multiepitope vaccine, comprising these antigens, could serve as a universal therapeutic vaccine for the vast majority of ovarian cancer patients.