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Background: Timing of initiation of screening for breast cancer is controversial in the United States.Objective: To determine the threshold relative risk (RR) at which the harm-benefit ratio of screening women aged 40 to 49 years equals that of biennial screening for women aged 50 to 74 years.Design: Comparative modeling study.Data Sources: Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and medical literature.Target Population: A contemporary cohort of women eligible for routine screening.Time Horizon: Lifetime.Perspective: Societal.Intervention: Mammography screening starting at age 40 versus 50 years with different screening methods (film, digital) and screening intervals (annual, biennial).Outcome Measures: Benefits: life-years gained, breast cancer deaths averted; harms: false-positive mammography findings; harm-benefit ratios: false-positive findings/life-years gained, false-positive findings/deaths averted.Results Of Base-case Analysis: Screening average-risk women aged 50 to 74 years biennially yields the same false-positive findings/life-years gained as biennial screening with digital mammography starting at age 40 years for women with a 2-fold increased risk above average (median threshold RR, 1.9 [range across models, 1.5 to 4.4]). The threshold RRs are higher for annual screening with digital mammography (median, 4.3 [range, 3.3 to 10]) and when false-positive findings/deaths averted is used as an outcome measure instead of false-positive findings/life-years gained. The harm-benefit ratio for film mammography is more favorable than for digital mammography because film has a lower false-positive rate.Results Of Sensitivity Analysis: The threshold RRs changed slightly when a more comprehensive measure of harm was used and were relatively insensitive to lower adherence assumptions.Limitation: Risk was assumed to influence onset of disease without influencing screening performance.Conclusion: Women aged 40 to 49 years with a 2-fold increased risk have similar harm-benefit ratios for biennial screening mammography as average-risk women aged 50 to 74 years. Threshold RRs required for favorable harm-benefit ratios vary by screening method, interval, and outcome measure.Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Background: Considerable effort has been expended on tobacco control strategies in the United States since the mid-1950s. However, we have little quantitative information on how changes in smoking behaviors have impacted lung cancer mortality. We quantified the cumulative impact of changes in smoking behaviors that started in the mid-1950s on lung cancer mortality in the United States over the period 1975-2000.Methods: A consortium of six groups of investigators used common inputs consisting of simulated cohort-wise smoking histories for the birth cohorts of 1890 through 1970 and independent models to estimate the number of US lung cancer deaths averted during 1975-2000 as a result of changes in smoking behavior that began in the mid-1950s. We also estimated the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking after the Surgeon General's first report on Smoking and Health in 1964.Results: Approximately 795,851 US lung cancer deaths were averted during the period 1975-2000: 552,574 among men and 243,277 among women. In the year 2000 alone, approximately 70,218 lung cancer deaths were averted: 44,135 among men and 26,083 among women. However, these numbers are estimated to represent approximately 32% of lung cancer deaths that could have potentially been averted during the period 1975-2000, 38% of the lung cancer deaths that could have been averted in 1991-2000, and 44% of lung cancer deaths that could have been averted in 2000.Conclusions: Our results reflect the cumulative impact of changes in smoking behavior since the 1950s. Despite a large impact of changing smoking behaviors on lung cancer deaths, lung cancer remains a major public health problem. Continued efforts at tobacco control are critical to further reduce the burden of this disease. [ABSTRACT FROM AUTHOR]

Purpose: This study compares HRQOL among subgroups of infants with asthma-like symptoms to a subgroup without such symptoms and examines independent associations between asthma-like symptoms during the first year of life and HRQOL at age 12 months.Methods: Our study sample included 5,000 infants participating in the Generation R study. Their parents completed structured questionnaires to obtain information on asthma-like symptoms, HRQOL, infants', and maternal characteristics. Asthma-like symptoms were defined according to the number of positive answers to 12 items on lower respiratory symptoms. HRQOL was measured using the ITQOL. Higher scores indicated better HRQOL.Results: Infants with asthma-like symptoms had significantly lower HRQOL scores for all ITQOL scales. Among the subgroup with severe symptoms (4% of the infants), relevant deficits in HRQOL were observed for most ITQOL scales, particularly for General Health, Bodily Pain, and Family Activities (effect sizes ≥ 0.8). In multivariate linear models, asthma-like symptoms were independently associated with 6 ITQOL scales. The population attributable risks were especially high for Family Activities, General Health, Parental Emotional, and Parental Time.Conclusions: Asthma-like symptoms during the first year of life are associated with impaired quality of life at age 12 months. At population level, asthma-like symptoms were associated with lower HRQOL, regardless of symptom severity. [ABSTRACT FROM AUTHOR]

Objective: This study examines the detection rates of suspected child abuse in the emergency departments of seven Dutch hospitals complying and not complying with screening guidelines for child abuse.Design: Data on demographics, diagnosis and suspected child abuse were collected for all children aged ≤18 years who visited the emergency departments over a 6-month period. The completion of a checklist of warning signs of child abuse in at least 10% of the emergency department visits was considered to be compliance with screening guidelines.Results: A total of 24 472 visits were analysed, 54% of which took place in an emergency department complying with screening guidelines. Child abuse was suspected in 52 children (0.2%). In 40 (77%) of these 52 cases, a checklist of warning signs had been completed compared with a completion rate of 19% in the total sample. In hospitals complying with screening guidelines for child abuse, the detection rate was higher (0.3%) than in those not complying (0.1%, p<0.001).Conclusion: During a 6-month period, emergency department staff suspected child abuse in 0.2% of all children visiting the emergency department of seven Dutch hospitals. The numbers of suspected abuse cases detected were low, but an increase is likely if uniform screening guidelines are widely implemented. [ABSTRACT FROM AUTHOR]

Dissemination of prostate-specific antigen (PSA) testing in the United States coincided with an increasing incidence of prostate cancer, a shift to earlier stage disease at diagnosis, and decreasing prostate cancer mortality. We compared PSA screening performance with respect to prostate cancer detection in the US population vs in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC-Rotterdam). We developed a simulation model for prostate cancer and PSA screening for ERSPC-Rotterdam. This model was then adapted to the US population by replacing demography parameters with US-specific ones and the screening protocol with the frequency of PSA tests in the US population. We assumed that the natural progression of prostate cancer and the sensitivity of a PSA test followed by a biopsy were the same in the United States as in ERSPC-Rotterdam. The predicted prostate cancer incidence peak in the United States was then substantially higher than the observed prostate cancer incidence peak (13.3 vs 8.1 cases per 1000 man-years). However, the actual observed incidence was reproduced by assuming a substantially lower PSA test sensitivity in the United States than in ERSPC-Rotterdam. For example, for nonpalpable local- or regional-stage cancers (ie, stage T1M0), the estimates of PSA test sensitivity were 0.26 in the United States vs 0.94 in ERSPC-Rotterdam. We conclude that the efficacy of PSA screening in detecting prostate cancer was lower in the United States than in ERSPC-Rotterdam. [ABSTRACT FROM AUTHOR]

We prospectively assessed trends in utilization and costs of diagnostic services of screen-positive women in a biennial breast cancer screening program for women aged 50-75 years. All 2,062 women with suspicious findings at screening mammography in the southern region of the Netherlands between 1 January 2000 and 1 July 2005 (158,997 screens) were included. Data were collected on any diagnostic examinations, interventional procedures, and surgical consultations with two-year follow-up. We used national reimbursement rates to estimate imaging costs and percutaneous biopsy costs. Cost prices, charged by hospitals, were used to estimate open surgical biopsy costs and surgical consultation costs. The largest increase in utilization of diagnostic procedures per 100 referrals was observed for axillary ultrasound (from 3.9 in 2000 to 33.5 in 2005) and for stereotactic core biopsy (from 2.1 in 2000 to 26.8 in 2005). Per 100 referrals, the open surgical biopsy rate decreased from 34.7 (2000) to 4.6 (2005) and the number of outpatient surgical consultations fluctuated between 269.8 (2000) and 309.7 (2004). Mean costs for the diagnosis of one cancer were Euro1,501 and ranged from Euro1,223 (2002) to Euro1,647 (2003). Surgical biopsies comprised 54.1% of total diagnostic costs for women screened in 2000, but decreased to 9.9% for women screened in 2005. Imaging costs increased from 23.7 to 43.8%, percutaneous biopsy costs from 9.9 to 27.2%, and consultation costs from 12.3 to 19.1%. We conclude that diagnostic costs per screen-detected cancer remained fairly stable through the years, although huge changes in the use of different diagnostic procedures were observed. [ABSTRACT FROM AUTHOR]

Objective: Children's fruit/vegetable intake is still below recommended levels. This study applied Internet-tailored advice for schoolchildren and Internet-supported brief dietary counselling (with child and parent) within preventive health care to promote fruit/vegetable intake.Setting/subjects: The study involved 30 seventh-grade classes (16 in the intervention group and 14 in the control group) with a total of 675 children aged 9-12 years, of whom 495 were allowed to participate.Design: A cluster-randomised baseline-post-test experimental design was applied. During school hours, all children completed Internet-administered questionnaires on fruit/vegetable intake and related determinants. Children in the intervention group received immediate online individually tailored nutrition feedback. For each child in the intervention group, a nurse received information concerning the assessment of fruit/vegetable intake via the Internet to support a 5 min counselling protocol to promote fruit/vegetable intake. Children completed a similar post-test questionnaire 3 months after the first assessment. Intention-to-treat analyses were conducted using multilevel regression analyses.Results: A total of 486 children (98% of 495) participated (263 in the intervention group, 223 in the control group); 240 child-parent couples in the intervention group attended the counselling. Awareness of inadequate fruit intake (odds ratio (OR) = 3.0; 95% confidence interval (CI) = 1.8-5.3) and knowledge of recommended vegetable intake levels (OR = 2.7; 95% CI = 1.8-4.1) were significantly more likely at post-test in the intervention group than in the control group. No significant effects were found on intake or other determinants.Conclusions: A compact, integrated two-component intervention can induce positive changes in knowledge and awareness of intake levels of fruit/vegetables among schoolchildren. To induce changes in intake levels, more comprehensive interventions may be needed. [ABSTRACT FROM AUTHOR]

Because the introduction of PSA testing has increased the reported incidence of prostate cancer, this study assessed the mental impact on men after receiving a diagnosis of prostate cancer. Participants in a prostate cancer screening trial (ERSPC) completed a questionnaire on health and, if diagnosed with prostate cancer, at two additional time points. In the pre-screening phase 3800 men (response 88%) completed the questionnaire. Of screen-diagnosed men (n=82) 52 (response 63%) completed two additional assessments. Gleason scores were < or=7 in 96% of men. Mental and self-rated overall health worsened significantly immediately after diagnosis (P < or=0.04). Six months later these scores improved and no longer differed significantly from the pre-diagnosis score. After obtaining a pre-diagnosis assessment in prospective prostate cancer patients we found a significant negative mental impact of prostate cancer diagnosis based on PSA testing. We recommend that clinicians share their knowledge on the generally favourable prognosis with their patients. The methodological implication is that considering a post-diagnosis assessment as 'baseline' may lead to an underestimation of the patient's mental health. [ABSTRACT FROM AUTHOR]

BACKGROUND: Belief that depression and other psychological factors predict breast cancer is common, but there have been few prospective epidemiological studies on this relationship. METHOD: The relationship between depression, personality traits, illness attitudes, life events and health history, and breast cancer risk was studied in a prospective, 6-9 year follow-up of a cohort study of 10892 Finnish women of 48-50 years of age at the baseline. Cancer cases were obtained from the Cancer Registry of Finland. Multivariate logistic regression analysis was performed controlling for socioeconomic factors, family history of cancer, parity, and health behaviours. RESULTS: Breast cancer incidence in the cohort was 1.15 times the average in age group 50-59. There was no evidence of depression, trait anxiety, cynical distrust, or coping being significant predictors of breast cancer incidence. CONCLUSION: In this cohort study with the 6-9 year follow-up, psychological factors such as depression, trait anxiety, cynical distrust, or coping did not increase breast cancer risk. [ABSTRACT FROM AUTHOR]

Adjuvant systemic therapy was introduced in the Netherlands as a breast cancer treatment in the early 1980s. In this paper, we describe the trends in the usage of adjuvant systemic treatment in the period 1975-1997 in the Netherlands. The main aim of our study was to assess the effects of adjuvant tamoxifen and polychemotherapy on breast cancer mortality, compared to the effects of the mammography screening programme. The computer simulation model MIcrosimulation SCreening ANalysis, which simulates demography, natural history of breast cancer and screening effects, was used to estimate the effects. Use of adjuvant therapy increased over time, but since 1990 it remained rather stable. Nowadays, adjuvant therapy is given to 88% of node-positive patients aged 50-69 years, while less than 10% of node-negative patients receive any kind of adjuvant treatment. Adjuvant treatment is given independent of the mode of detection (adjusted by nodal status and size). We predict that the reduction in breast cancer mortality due to adjuvant therapy is 7% in women aged 55-74 years, while the reduction due to screening, which was first implemented in women aged 50-69 years in 1990-97, will be 28-30% in 2007. In conclusion, although adjuvant systemic therapy can reduce breast cancer mortality rates, it is anticipated to be less than the mortality reduction caused by mammography screening.British Journal of Cancer (2004) 91, 242-247. doi:10.1038/sj.bjc.6601969 www.bjcancer.com Published online 22 June 2004 [ABSTRACT FROM AUTHOR]

The effectiveness of intensive surveillance in women at high risk for breast cancer due to a familial or genetic predisposition is uncertain and is currently being evaluated in a Dutch magnetic resonance imaging (MRI) screening (MRISC) study, in which annual imaging consists of mammography and MRI. Unfavourable side effects on health-related quality of life may arise from this screening process. We examined the short-term effects of screening for breast cancer in high-risk women on generic health-related quality of life and distress. A total of 519 participants in the MRISC study were asked to complete generic health-status questionnaires (SF-36, EQ-5D) as well as additional questionnaires for distress and items relating to breast cancer screening, at three different time points around screening. The study population showed significantly better generic health-related quality of life scores compared to age-/sex-adjusted reference scores from the general population. Neither generic health-related quality of life scores nor distress scores among the study sample (n=334) showed significant changes over time. The impact of the screening process on generic health status did not differ between risk categories. Relatively more women reported mammography as quite to very painful (30.1%) compared to MRI. Anxiety was experienced by 37% of the women undergoing MRI. We conclude that screening for breast cancer in high-risk women does not have an unfavourable impact on short-term generic health-related quality of life and general distress. In this study, high-risk women who opted for regular breast cancer screening had a better health status than women from the general population.British Journal of Cancer (2004) 91, 69-76. doi:10.1038/sj.bjc.6601912 www.bjcancer.com Published online 15 June 2004 [ABSTRACT FROM AUTHOR]

Background: Screening for prostate cancer advances the time of diagnosis (lead time) and detects cancers that would not have been diagnosed in the absence of screening (overdetection). Both consequences have considerable impact on the net benefits of screening.Methods: We developed simulation models based on results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified, and on baseline prostate cancer incidence and stage distribution data. The models were used to predict mean lead times, overdetection rates, and ranges (corresponding to approximate 95% confidence intervals) associated with different screening programs.Results: Mean lead times and rates of overdetection depended on a man's age at screening. For a single screening test at age 55, the estimated mean lead time was 12.3 years (range = 11.6-14.1 years) and the overdetection rate was 27% (range = 24%-37%); at age 75, the estimates were 6.0 years (range = 5.8-6.3 years) and 56% (range = 53%-61%), respectively. For a screening program with a 4-year screening interval from age 55 to 67, the estimated mean lead time was 11.2 years (range = 10.8-12.1 years), and the overdetection rate was 48% (range = 44%-55%). This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4% to 10.6%, a relative increase of 65% (range = 56%-87%). In annual screening from age 55 to 67, the estimated overdetection rate was 50% (range = 46%-57%) and the lifetime prostate cancer risk was increased by 80% (range = 69%-116%). Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinically relevant cancer detected.Conclusions: These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year. [ABSTRACT FROM AUTHOR]

Background: Population-based screening for prostate cancer is currently being evaluated in randomized clinical trials in the United States and in Europe. Side effects arising from the process of screening and from the earlier treatment of screen-detected prostate cancer may be important factors in the evaluation. To examine health-related quality of life (or health status) among men screened for prostate cancer, we conducted a longitudinal study of 626 attenders to the Rotterdam (The Netherlands) prostate cancer screening program and of 500 nonparticipants.Methods: Attenders of the screening program and nonparticipants completed self-assessment questionnaires (SF-36 [i.e., Medical Outcomes Study 36-Item Short-Form Health Survey] and EQ-5D [i.e., EuroQol measure for health-related quality of life] health surveys) to measure generic health status, as well as an additional questionnaire for anxiety and items relating to prostate cancer screening.Results: Physical discomfort during digital rectal examination and during transrectal ultrasound was reported by 181 (37%) of 491 men and by 139 (29%) of 487 men, respectively; discomfort during prostate biopsy was reported by 64 (55%) of 116 men. Mean scores for health status and anxiety indicated that the participants did not experience relevant changes in physical, psychological, and social functioning during the screening procedure. However, high levels of anxiety were observed throughout the screening process among men with a high predisposition to anxiety. Similar scores for anxiety predisposition were observed among attenders and nonparticipants.Conclusions: At the group level, we did not find evidence that prostate cancer screening induced important short-term health-status effects, despite the short-lasting side effects related to the biopsy procedure. However, subgroups may experience high levels of anxiety. The implication is that unfavorable health-status effects of prostate cancer screening occur mainly in the treatment phase. [ABSTRACT FROM AUTHOR]

Background: Results from five Swedish randomized trials may provide the most conclusive evidence on the effect of mammographic screening and have been used to forecast the expected reduction in breast cancer mortality in other programs. However, those trials demonstrated different degrees of reduction. The interpretation of observed mortality reduction after long follow-up for women aged 40-49 years at trial entry is both important and controversial.Purpose: We estimated what percentage of the observed mortality reduction for women aged 40-49 years at entry into the five Swedish screening trials might be attributable to screening these women at 50 years of age or older. Moreover, we calculated the most likely percentage mortality reduction for specific screening programs if the Swedish results were generalized and analyzed whether characteristics of each trial might at least partly explain the observed differences in reductions among the trials.Methods: Each Swedish trial was simulated with one underlying computer simulation model (MISCAN--MIcrosimulation SCreening ANalysis) of the natural history of the disease and the performance of screening, taking into account nine important trial characteristics. Improvement in prognosis for screen-detected case patients was estimated with age-specific reduction for all trials and each trial design as a reference.Results: An expected 7% reduction in breast cancer mortality for women aged 40-49 years at trial entry (relative risk [RR] = 0.93) was determined by computer modeling, assuming no improvement in prognosis for cancers that are screen detected before 50 years of age. This result indicates that, of the overall 10% observed reduction (RR = 0.90) in the five Swedish trials analyzed, most (70%) of this reduction might be attributable to screening these women in later rounds after their 50th birthday. Using additional trial information, predictions of breast cancer mortality reduction in women 50 years or older might be 11% larger than previously expected, assuming that high-quality mammographic screening can be achieved in nationwide programs. For women aged 50-69 years at trial entry, the differences in expected versus observed mortality reduction among the trials are estimated to be relatively small. (Expected mortality reductions range from 24% to 32%).Conclusions: Results from the Swedish randomized breast cancer-screening trials should be seen as more favorable regarding the effect of mammographic screening in reducing breast cancer mortality for women aged 50-69 years than was estimated earlier. Our analyses also suggest that the improvement in prognosis due to screening for women aged 40-49 years is much smaller than that for women aged 50 years or older. Approximately, 70% of the 10% observed reduction in breast cancer mortality (i.e., 7%) for women aged 40-49 years at trial entry might be attributable to a reduction due to screening these women after they reach age 50.Implications: Detailed screening data for the 40- to 49-year age group of all Swedish trials should be analyzed to specifically estimate the natural history and performance of screening in this age group. [ABSTRACT FROM AUTHOR]

Background: the effects and costs of different policies for breast cancer screening in Catalonia (Spain) were analysed, to give a basis for setting priorities and deciding on the introduction of a screening programme. Methods: the MISCAN (MIcrosimulation SCreening ANalysis) model of the natural history of breast cancer was used. The epidemiology of breast cancer in Catalonia and the demography of the Catalan population was taken into account as well as the results on mortality reduction from a Swedish overview of breast cancer screening trials. Results: the reduction in breast cancer mortality in the total female population due to a screening programme for the age group 50-64 years would be 16, 12 and 9%, with screening intervals of one, two and three years respectively. The cost-effectiveness ratios (CE ratios) for these scenarios were 924,000, 730,000 and 719,000 pesetas (PO per life-year gained respectively (5% discounting). The most cost-effective screening scenario is the one in which women aged 50-69 years are screened with an interval of three years with a mortality reduction of approximately 12% in the total female population (CE ratio = 694,000 Pt). Screening until the age of 69 years (two year interval) was almost as cost-effective as screening the age group 50-64 years with a two year interval, with a reduction in breast cancer mortality of 15%. Extension to under the age of 50 years resulted in diverging results depending on the assumptions for improvement in prognosis for younger women (40-49 years). Conclusion: if the extension of a two yearly screening programme for women aged 50-64 years is considered (mortality reduction of 12%), extension to older women would be more advisable, based on proven benefits and costs, than extension to younger age groups. [ABSTRACT FROM AUTHOR]

Primary prostate cancer treatment often results in suboptimal urinary, bowel and/or sexual function. These effects are not inevitable. After treatment patients typically report high health related quality of life (QoL) scores. This discrepancy between disease-specific and generic results raises the question which meaning side effects actually have to patients. In a qualitative study we explored two mechanisms which could possibly explain the discrepancy: insensitivity of generic QoL measures to these specific symptoms and adaptation to changed health (response shift). In semi-structured interviews with 33 prostate cancer patients in the Netherlands we collected data on their opinions regarding health and QoL, we observed how respondents behaved when completing health status and QoL questionnaires, and solicited comments on a QoL questionnaire, its items, and its content validity. We observed that patients trivialized sexual (dys) function referring to old age. We found that while they might consider sexual, urinary, and bowel dysfunctions as problems, they did not take such dysfunctions into account when completing QoL measures because they did not view these dysfunctions as aspects of health. This finding reveals a so far unidentified cause of the insensitivity of generic measures of health status. Furthermore, response shift appeared to be present: many patients accepted the side effects as inevitable consequences of having been treated for prostate cancer, a condition they perceived as life threatening. We conclude that generic QoL measures cannot reveal the impact of sexual, urinary and bowel dysfunctions on patients because such dysfunctions are not perceived as health problems. By presenting these findings we want to draw attention to issues that complicate QoL assessments in general and in prostate cancer patients in particular. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the content of decision-relevant knowledge needed for informed decision-making about (non-) participation in prenatal screening for Down's syndrome (DS), in order to develop a knowledge questionnaire for routine application in large-scale programme evaluations. METHODS: A generic list of content domains for knowledge about screening was extracted from the literature. Items reflecting specific knowledge domains were constructed. An expert group of professionals and pregnant women expressed whether domains and items represented decision-relevant information. RESULTS: All presented domains were scored as (very) important. Options when receiving an 'increased probability for DS' test result, the meaning of this result, the aim of the screening, and voluntary nature of the test were scored as most important. The condition being screened for, prevalence, and the screening procedure were scored as relatively less important, with a high amount of expert consensus. CONCLUSION: A knowledge measure for prenatal screening for DS was developed, based on domains and items acquired by expert consensus. PRACTICE IMPLICATIONS: This measure of decision-relevant knowledge can be used in routine, large-scale evaluations of the procedure for offering information about prenatal screening for DS. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is believed that making an informed decision about (screening) participation is associated with better health-related quality of life (HRQoL) outcomes. This is the first study in cancer screening to explore this association in subjects participating in a lung cancer computed tomography (CT) screening trial. Methods: Participants that made either an informed decision to participate (n =155) or not (n =133) were selected for this study. Differences in HRQoL, measured as generic HRQoL (Short Form 12 [SF-12] and EuroQol questionnaire [EQ-5D]), anxiety/distress (State-Trait Anxiety Inventory [STAI-6], Impact of Event Scale [IES] and Consequences of Screening-Lung Cancer [COS-LC]), were tested with Mann–Whitney U tests and ANOVA at three assessment points (when deciding about participation, before trial randomisation and 2months after receiving the CT result). Results: Subjects who made an informed decision to participate had no better scores than those who did not make an informed decision for 23 out of 24 HRQoL comparisons, except for a better mean score for mental health (Mental Component Summary (MCS)=53.9±9.2 versus 51.0±10.1, p =0.003) before randomisation. For subjects with an indeterminate CT result (n =64), no significant differences were found between subjects with (n =35) or without (n =29) an informed decision. Conclusion: Subjects who did not make an informed decision to participate in lung cancer CT screening trial did not experience worse HRQoL during screening than subjects who did make an informed decision, either in general or after receiving an indeterminate result. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified pulmonary nodules. Material and Methods: This study was institutional review board approved. For this study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50mm3) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer. Results: Of the 469 nodules, 387 (83%) were between 50 and 500mm3, 82 (17%) >500mm3, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103mm3 (range 50-5486mm3). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32-0.43). Conclusion: In solid non-calcified nodules larger than 50mm3, size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power. [ABSTRACT FROM AUTHOR]

Background: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women. Methods: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups. Results: We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups. Conclusions: MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer. [ABSTRACT FROM AUTHOR]

Background: More than a decade ago, a mammography screening programme for women aged 50-69 years was initiated in the Netherlands. Our aim was to assess the effect of this programme on breast-cancer mortality rates.Methods: We examined data for 27948 women who died of breast-cancer aged 55-74 years between 1980 and 1999 (30560 cases until 2001). We grouped individuals into 93 clusters, depending on where they lived, and analysed data by use of national population statistics. We analysed time trends in breast-cancer mortality, adjusting for gradual implementations at municipality level, taking as year 0 the month and year in which screening began in a particular municipality. We used a Poisson regression model to estimate the time at which the trend started to turn. We assessed indirectly whether this turning point was related to initiation of screening or adjuvant systemic therapy in four clusters defined according to when screening was implemented.Findings: Compared with rates in 1986-88, breast-cancer mortality rates in women aged 55-74 years fell significantly in 1997 and subsequent years as predicted, reaching -19.9% in 2001. Mortality rates had been increasing by an annual 0.3% until screening was introduced; thereafter we noted a decline of 1.7% per year (95% CI 2.39-0.96) in women aged 55-74 years and of 1.2% in those aged 45-54 (2.40 to 0.07). The turning point in mortality trends arose at around year 0. Adjuvant systemic therapy is unlikely to be the cause of this turning point, since the mortality rates continued to rise up to 1 year after implementation in municipalities where screening began after 1995.Interpretation: Routine mammography screening can reduce breast-cancer mortality rates in women aged 55-74 years. [ABSTRACT FROM AUTHOR]

Aim: Lung cancer growth rate influences screening strategies and treatment decisions. This review aims to provide an overview of primary lung cancer growth rate, quantified by volume doubling time (VDT) through computed tomography (CT) measurement., Methods: Using PRISMA-DTA guideline, PubMed, EMBASE, and Web of Science were searched until March 2024 for studies reporting CT-measured VDT of pathologically confirmed primary lung cancer before intervention. Summary data were extracted from published reports by two independent researchers. Primary outcomes were pooled mean VDT of lung cancer by nodule type and histology, distribution of indolent lung cancer (defined as VDT>400 days or negative), and correlated factors., Results: Thirty-three studies were eligible, comprising 3959 patients with primary lung cancer (mean age range:57.6-77.0 years; 60.0 % men). The pooled mean VDT for solid, part-solid, and nonsolid lung cancer were 207, 536, and 669 days, respectively (p < 0.001). When stratified by histology within solid lung cancer, the pooled mean VDT of adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and others were 223, 140, 73, and 178 days, respectively (p < 0.001). Indolent lung cancer was observed in 34.9 % of lung cancer, predominantly in adenocarcinoma (68.9 %). Adenocarcinoma was associated with slower growth, whereas factors such as tumor size, solidity, TNM staging, and smoking history were positively associated with growth rates., Conclusions: Pooled mean VDT of solid lung cancer was approximately 207 days, demonstrating significant variability in histology yet remaining under the 400-day referral threshold. Key predictors of growth rate include histology, size, solidity, and smoking history, essential for tailoring early intervention strategies., Trial Registration Number: CRD42023408069., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Importance: Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts., Objective: To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density., Design, Setting, and Participants: Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data. Simulated women born in 1980 with average breast cancer risk were included. Modeling analyses were conducted from January 2020 to December 2023., Intervention: Annual or biennial mammography screening with or without supplemental MRI by breast density starting at ages 40, 45, or 50 years through age 74 years., Main Outcomes and Measures: Lifetime breast cancer deaths averted, false-positive recall and false-positive biopsy recommendations per 1000 simulated women followed-up from age 40 years to death summarized as means and ranges across models., Results: Biennial DBT screening for all simulated women started at age 50 vs 40 years averted 7.4 vs 8.5 breast cancer deaths, respectively, and led to 884 vs 1392 false-positive recalls and 151 vs 221 false-positive biopsy recommendations, respectively. Biennial digital mammography had similar deaths averted and slightly more false-positive test results than DBT screening. Adding MRI for women with extremely dense breasts to biennial DBT screening for women aged 50 to 74 years increased deaths averted (7.6 vs 7.4), false-positive recalls (919 vs 884), and false-positive biopsy recommendations (180 vs 151). Extending supplemental MRI to women with heterogeneously or extremely dense breasts further increased deaths averted (8.0 vs 7.4), false-positive recalls (1088 vs 884), and false-positive biopsy recommendations (343 vs 151). The same strategy for women aged 40 to 74 years averted 9.5 deaths but led to 1850 false-positive recalls and 628 false-positive biopsy recommendations. Annual screening modestly increased estimated deaths averted but markedly increased estimated false-positive results., Conclusions and Relevance: In this model-based comparative effectiveness analysis, supplemental MRI for women with dense breasts added to DBT screening led to greater benefits and increased harms. The balance of this trade-off for supplemental MRI use was more favorable when MRI was targeted to women with extremely dense breasts who comprise approximately 10% of the population.

Aims: Evidence on the impact of screening for cardiovascular diseases (CVDs) on health-related quality of life (HRQoL) is important for policy decisions about screening implementation and to uncover teachable moments to motivate healthy lifestyle choices. It is unknown whether screening by cardiac computed tomography (CT) scan has a stronger impact on HRQoL than screening by traditional risk prediction models. The study aims to investigate differences in HRQoL across the screening process between participants who were randomized to CVD risk estimation by coronary artery calcium score or Systematic COronary Risk Evaluation., Methods and Results: A subset of 2687 ROBINSCA participants filled in questionnaires at (T0) randomization, (T1) invitation, (T2) 1-3 days before screening, (T3) 1-3 days after, and (T4) screening result. Generic HRQoL (SF-12; EQ-5D) and anxiety (STAI-6) were measured. We investigated the differences in changes in HRQoL across the screening process with linear mixed models. We found comparable levels of HRQoL at all screening moments for the two intervention groups. Mental health scores were worse at invitation and randomization than at the later time points, irrespective of screening group (all P < 0.001). A result indicating a heightened CVD risk was associated with increased anxiety in the CT screening group., Conclusion: Computed tomography screening for CVD risk has no detrimental impact on HRQoL and anxiety levels compared to screening by traditional risk assessment. Receiving an invitation to screenning or a result implying increased CVD risk could function as teachable moments for high-risk individuals., Registration: ROBINSCA trial registration number: NTR6471 in Dutch Trial Register (NTR)., Competing Interests: Conflict of interest: D.M. reports grants from European Commission—Horizon 2020, outside the conduct of this study. H.J.K. reports an advanced grant from the European Research Council during conduct of the study and grants from European Commission—Horizon 2020, outside the conduct of the study. M.V. reports supports for attending meetings and travel by the British Society of Cardiovascular Imaging, outside of the conduct of this study. R.V. reports grants from Siemens, the Dutch Heart Foundation, The Netherlands Organisation for Health Research and Development, and the Dutch Cancer Foundation, outside the conduct of this study. C.M.v.d.A. reports grants from the European Research Council during conduct of the study and fiduciary role in the B3 user commitee outside the conduct of the study. The authors have no other conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Breast cancer (BC) screening enables early detection of BC, which may lead to improved quality of life (QoL). We aim to compare QoL between women with a screen-detected and clinically detected BC in the Netherlands., Methods: We used data from the 'Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation' (UMBRELLA) between October 2013 and March 2022. Patients were categorized as screen-detected or clinically detected. We analysed three questionnaires, namely EORTC QLQ C-30, BR23, and HADS (Hospital Anxiety and Depression Scale) completed by BC patients shortly after diagnosis (T1) and one-year after treatment (T2). Independent t-tests were performed to compare QoL average differences between the two groups. Bonferroni-corrected p-value significance threshold of 0.00057 was used. The magnitude of differences was calculated using Cohen's d. The clinical relevance of QLQ-C30 differences was assessed based on interpretation guideline of EORTC-QLQ-C30 results., Results: After applying inclusion and exclusion criteria, there were 691 women with screen-detected BC and 480 with clinically detected BC. Generally, screen-detected BC patients reported a better QoL. At T1, their average QLQ-C30 summary score was higher (86.1) than clinically detected BC patients (83.0) (p < 0.0001). Cohen's d for all items ranged between 0.00 and 0.39. A few QLQ-C30 score differences were clinically relevant, indicating better outcomes in emotional functioning, general health, constipation, and fatigue for women with screen-detected BC., Conclusions: In the Netherlands, women with screen-detected BC reported statistically significant and better QoL than women with clinically detected BC. However, clinical relevance of the differences is limited., (© 2024. The Author(s).)

Introduction: Lung cancer is a leading cause of mortality worldwide, with lung cancer treatment presenting a significant financial burden. The treatment landscape has recently shifted, seeing an increase in targeted- and immunotherapies. Such treatments are expensive, but estimates of the medical costs of the lung cancer treatment pathway largely predate their introduction., Methods: We link medical expenditures of individuals resident in the Netherlands (n = 19.2 m) for 2013-2021 to tumour-level (n = 137,129, incident 2012-2021) Netherlands Cancer Registry data. We estimate lung cancer-attributable costs by phase of care (initial, continuing and terminal), stratified by cancer stage and histology, and observe trends in medical costs over time., Results: We estimate mean costs over the lung cancer treatment pathway to be €48,443 per patient. Total medical costs are highest in the initial phase, followed by the terminal and continuing phase. Monthly treatment for stage IV lung cancer is significantly more expensive than for early-stage disease (€8293 per month of initial care relative to €3228 for stage IA). Stage IV lung cancer has become significantly more expensive to treat 2018-2021 relative to 2013-2017, with monthly expenditures rising 55 % in initial care and 148 % in continuing care. Population-wide, we find €900.6 million spent on lung cancer care in 2021, €433 million more than in 2016, of which €307.3 million is attributed to per-patient expenditure trends., Conclusions: Treatment advances are quickly inflating medical costs for late-stage lung cancer. Policy makers should carefully evaluate the cost-effectiveness of novel treatments, and incorporate stage-specific treatment costs in evaluating interventions for early detection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Many countries have incorporated population screening programmes for cancer, such as colorectal and lung cancer, into their health-care systems. Cirrhosis is more prevalent than colorectal cancer and has a comparable age-standardized mortality rate to lung cancer. Despite this fact, there are no screening programmes in place for early detection of liver fibrosis, the precursor of cirrhosis. In this Perspective, we use insights from colorectal and lung cancer screening to explore the benefits, challenges, implementation strategies and pathways for future liver fibrosis screening initiatives. Several non-invasive methods and referral pathways for early identification of liver fibrosis exist, but in addition to accurate detection, screening programmes must also be cost-effective and demonstrate benefit through a reduction in liver-related mortality. Randomized controlled trials are needed to confirm this. Future randomized screening trials should evaluate not only the screening tests, but also interventions used to halt disease progression in individuals identified through screening., (© 2024. Springer Nature Limited.)

Background: Recommendations regarding personalized lung cancer screening are being informed by natural-history modeling. Therefore, understanding how differences in model assumptions affect model-based personalized screening recommendations is essential., Design: Five Cancer Intervention and Surveillance Modeling Network (CISNET) models were evaluated. Lung cancer incidence, mortality, and stage distributions were compared across 4 theoretical scenarios to assess model assumptions regarding 1) sojourn times, 2) stage-specific sensitivities, and 3) screening-induced lung cancer mortality reductions. Analyses were stratified by sex and smoking behavior., Results: Most cancers had sojourn times <5 y (model range [MR]; lowest to highest value across models: 83.5%-98.7% of cancers). However, cancer aggressiveness still varied across models, as demonstrated by differences in proportions of cancers with sojourn times <2 y (MR: 42.5%-64.6%) and 2 to 4 y (MR: 28.8%-43.6%). Stage-specific sensitivity varied, particularly for stage I (MR: 31.3%-91.5%). Screening reduced stage IV incidence in most models for 1 y postscreening; increased sensitivity prolonged this period to 2 to 5 y. Screening-induced lung cancer mortality reductions among lung cancers detected at screening ranged widely (MR: 14.6%-48.9%), demonstrating variations in modeled treatment effectiveness of screen-detected cases. All models assumed longer sojourn times and greater screening-induced lung cancer mortality reductions for women. Models assuming differences in cancer epidemiology by smoking behaviors assumed shorter sojourn times and lower screening-induced lung cancer mortality reductions for heavy smokers., Conclusions: Model-based personalized screening recommendations are primarily driven by assumptions regarding sojourn times (favoring longer intervals for groups more likely to develop less aggressive cancers), sensitivity (higher sensitivities favoring longer intervals), and screening-induced mortality reductions (greater reductions favoring shorter intervals)., Implications: Models suggest longer screening intervals may be feasible and benefits may be greater for women and light smokers., Highlights: Natural-history models are increasingly used to inform lung cancer screening, but causes for variations between models are difficult to assess.This is the first evaluation of these causes and their impact on personalized screening recommendations through easily interpretable metrics.Models vary regarding sojourn times, stage-specific sensitivities, and screening-induced lung cancer mortality reductions.Model outcomes were similar in predicting greater screening benefits for women and potentially light smokers. Longer screening intervals may be feasible for women and light smokers., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kevin ten Haaf reports grants from NIH, the Dutch Research Council, the EU, University of Zurich, Cancer Research UK, Cancer Australia, the Medical Services Advisory Committee of the Australian Ministry of Health and Erasmus University Medical Center Rotterdam/Erasmus University Rotterdam/Technical University of Delft; honoraria from CHUV: Centre Hospitalier Universitaire Vaudois and Johnson&Johnson paid to his institution and support for traveling and lodging fees from CHUV and Rescue Lung Society. Koen de Nijs reports grants from NIH, the EU, and University of Zurich; Pianpian Cao reports grants from NIH; Iakovos Toumazis reports grants from NIH; G. Scott Gazelle reports grants from NIH; Chung Ying Kong reports grants from NIH; Sylvia Plevritis reports grants from NIH, NCI, and ACED, consulting fees from Adela Biosciences, support from attending meetings and/or travel from NCI and advisory board memberships for NCI, Knight Cancer Center, and the Ontario Institute for Cancer Research; Rafael Meza reports grants from NIH; Harry de Koning reports honoraria for lectures for TEVA/Menarini/Astra Zeneca and external reviews for Bayer. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided in part by grants U01CA199284 from the National Cancer Institute (NCI) and VENI grant from the Dutch Research Council/Netherlands Organization of Health Research (ZonMW) (grant No. 09150161910060). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by NCI. OncoSim is led and supported by the Canadian Partnership Against Cancer, with model development by Statistics Canada, and is made possible through funding from Health Canada. The assumptions and calculations underlying the simulation results were prepared by the authors, and the responsibility for the use and interpretation of these data and their reporting is entirely that of the authors.