Screening Arm Research Articles

Economic Burden Conferred by Population-Level Cancer Screening on Resource-Limited Communities: Lessons From the ESECC Trial.

ObjectivesUpper gastrointestinal (G.I.) cancer screening has been conducted in China for decades. However, the economic burden for treatment “intensively” occurred in advance due to screening in resource-limited communities remain unclear.MethodsWe compared the treatment costs for upper G.I. cancers from the screening and control arms of a population-based randomized trial in a high-risk area for esophageal cancer (EC) in China based on claims data from the health insurance system in the local area which included whole population coverage.ResultsThe average out-of-pocket cost per treatment of EC in the screening arm was lower than that in the control arm ($5,972 vs. $7,557). This difference was a consequence of down-staging from screening which resulted in lower cost therapy for earlier stage cancers. Moreover, this result is similar for cardial and non-cardial gastric cancer in the two study arms ($7,933 vs. $10,605). However, three times as many (103 vs. 36) families in the screening arm suffered catastrophic health expenditure for all cancer types. The overall treatment cost for all EC patients in the screening arm ($1,045,119) was 2.44 times that in the control arm ($428,292), and the ratio for cardial and non-cardial gastric cancer was 1.12 ($393,261 vs. $351,557).ConclusionCancer treatment secondary to screening may triple the likelihood of catastrophic patient medical expenditure, and sharply increase the economic pressure on the local community, particularly for cancer types which are of high prevalence. Financial support for patients and the health insurance system should be taken into consideration when planning budgets for cancer screening programs in communities which are resource-limited.

Screening for Atrial Fibrillation in Older Adults at Primary Care Visits: VITAL-AF Randomized Controlled Trial.

Undiagnosed atrial fibrillation (AF) may cause preventable strokes. Guidelines differ regarding AF screening recommendations. We tested whether point-of-care screening with a handheld single-lead ECG at primary care practice visits increases diagnoses of AF. We randomized 16 primary care clinics 1:1 to AF screening using a handheld single-lead ECG (AliveCor KardiaMobile) during vital sign assessments, or usual care. Patients included were ages ≥65 years. Screening results were provided to primary care clinicians at the encounter. All confirmatory diagnostic testing and treatment decisions were made by the primary care clinician. New AF diagnoses during the 1-year follow-up were ascertained electronically and manually adjudicated. Proportions and incidence rates were calculated. Effect heterogeneity was assessed. Of 30 715 patients without prevalent AF (n=15 393 screening [91% screened], n=15 322 control), 1.72% of individuals in the screening group had new AF diagnosed at 1 year versus 1.59% in the control group (risk difference, 0.13% [95% CI, -0.16 to 0.42]; P=0.38). In prespecified subgroup analyses, new AF diagnoses in the screening and control groups were greater among those aged ≥85 years (5.56% versus 3.76%, respectively; risk difference, 1.80% [95% CI, 0.18 to 3.30]). The difference in newly diagnosed AF between the screening period and the previous year was marginally greater in the screening versus control group (0.32% versus -0.12%; risk difference, 0.43% [95% CI, -0.01 to 0.84]). The proportion of individuals with newly diagnosed AF who were initiated on oral anticoagulants was not different in the screening (n=194, 73.5%) and control (n=172, 70.8%) arms (risk difference, 2.7% [95% CI, -5.5 to 10.4]). Screening for AF using a single-lead ECG at primary care visits did not affect new AF diagnoses among all individuals aged 65 years or older compared with usual care. URL: https://www. gov; Unique identifier: NCT03515057.

A randomized trial of risk-adapted screening for prostate cancer in young men-Results of the first screening round of the PROBASE trial.

There is no generally accepted screening strategy for prostate cancer (PCa). From February 2014 to December 2019 a randomized trial (PROBASE) recruited 46 642 men at age 45 to determine the efficacy of risk-adapted prostate-specific antigen-based (PSA) screening, starting at either 45 or 50 years. PSA tests are used to classify participants into a low (<1.5ng/mL), intermediate (1.5-2.99 ng/mL) or high (≥3ng/mL) risk group. In cases of confirmed PSA values ≥3ng/mL participants are recommended a prostate biopsy with multiparametric magnetic resonance imaging (mpMRI). Half of the participants (N=23 341) were offered PSA screening immediately at age 45; the other half (N=23 301) were offered digital rectal examination (DRE) with delayed PSA screening at age 50. Of 23 301 participants who accepted baseline PSA testing in the immediate screening arm, 89.2% fell into the low, 9.3% into intermediate, and 1.5% (N=344) into the high risk group. Repeat PSA measurement confirmed high-risk status for 186 men (0.8%), of whom 120 (64.5%) underwent a biopsy. A total of 48 PCas was detected (overall prevalence 0.2%), of which 15 had International Society of Uropathology (ISUP) grade 1, 29 had ISUP 2 and only 4 had ISUP ≥3 cancers. In the delayed screening arm, 23 194 participants were enrolled and 6537 underwent a DRE with 57 suspicious findings, two of which showed PCa (both ISUP 1; detection rate 0.03%). In conclusion, the prevalence of screen-detected aggressive (ISUP ≥3) PCa in 45-year-old men is very low. DRE did not turn out effective for early detection of PCa.

Abstract OT2-10-02: Mypebs: An international randomized study comparing personalized, risk-stratified to standard breast cancer screening in women aged 40-70

Abstract Background Currently, mammographic-based breast cancer screening (BCS) using age as the single criterion for population selection, apart from rare high-risk indications, is being questioned for its imperfect sensitivity (interval cancers) and specificity (false positive recalls), as well as the risk of over-diagnoses. BC risk scores incorporating personal and family history, breast mammographic density and genetic information based on a polygenic score (PRS) give a promisingly accurate likelihood of a woman developing invasive BC in the next 5 years. MyPeBS, a European Commission H2020-funded randomized clinical trial (NCT03672331) conducted in 6 countries (Belgium, France, Israel, Italy, Spain and UK) aims to demonstrate the usefulness of a risk-based screening approach to improve BCS in the general population. Methods MyPeBS’s primary objective is to show non-inferiority of the risk-stratified BCS arm in terms of incidence rate of breast cancer of stage 2 and higher, compared to the standard BCS arm. The key secondary objective, if non-inferiority is shown, is to demonstrate superiority of the risk-based screening arm. MyPeBS also assesses whether this strategy allows reduces morbidity (less false positives); is equally or more cost-effective, and impacts women’s understanding, awareness and emotional responses as compared to standard of care. Women aged 40 to 70 are eligible if they did not have prior BC or high risk-condition, and live in a participating country and area. Participants are randomized 1:1 between standard BCS according to country’s/region’s ongoing policy, or risk-stratified BCS, where screening frequency and method depend on their individual 5 year predicted risk of invasive BC (Table 1). Stratification factors include age, prior mammogram and country. Risk assessment uses a centralized genotyping on a saliva sample to assess PRS 313 (Mavaddat et al, Am J Hum Genet 2019), which is embedded in either a BCSC-derived score for women with at most one first-degree relative with BC; or Tyrer-Cuzick score for women with &amp;gt; 1 family member with breast cancer. Women participate for 4 years. Planned accrual is 85000. On June 30th, 2021, 13882 women have been randomized. Table 1.BC Screening schedule in MyPeBS’ Risk-based armRisk levelLow riskAverage riskHigh riskVery high riskNumerical definition (invasive breast cancer risk at 5 years)&amp;lt;1%1-1.66%≥ 1.66% and &amp;lt; 6%≥ 6%Mammogram1 at end of study (4 years)Every 2 yearsYearlyYearlyAdditionalYearly breast cancer awareness reminderHigh density: US or ABUS every 2 yearsHigh density: US or ABUS every 2 yearsAnnual MRI until age 60 Citation Format: Suzette Delaloge, Paolo Giorgi Rossi, Michal Guindy, Fiona Gilbert, Jean-Benoit Burrion, Corinne Balleyguier, Marta Roman Exposito, Livia Giordano, Harry De Koning, Sandrine de Montgolfier, Stephane Ragusa, Damien Drubay, Marie-Eve Rouge-Bugat, Gareth D Evans, Debbie Keatley, Helene Blanche, Anne Boland, Emilien Gauthier, Aloys Dubois d'Aische, Cécile Vissac-Sabatier, Daniel Couch, Camille Baron, Jean-François Deleuze, Paul Pharoah, Stefan Michiels. Mypebs: An international randomized study comparing personalized, risk-stratified to standard breast cancer screening in women aged 40-70 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-10-02.

The Association Between Age, Prostate Cancer Risk, and Higher Gleason Score in a Long-term Screening Program: Results from the Göteborg-1 Prostate Cancer Screening Trial

BackgroundStudies have suggested associations between greater age, increased risk of prostate cancer (PC), and higher Gleason score. ObjectiveThe present study aimed at investigating these associations within the Göteborg-1 randomized, population-based PC screening trial. Design, setting, and participantsThe screening arm of the Göteborg-1 screening trial comprises 10000 randomly selected men (aged 50–64 yr at randomization) from the Göteborg region of Sweden. Between 1995 and 2014, they were biennially invited to prostate-specific antigen (PSA) testing to an upper age limit of 70 yr (range 67–71 yr). PSA ≥3 ng/ml triggered a prostate biopsy (sextant biopsy 1995–2009, thereafter a ten-core biopsy). Outcome measurements and statistical analysisThe impact of age on Gleason score, given a screen-detected PC, was investigated with multinomial logistic regression analyses adjusted for year of testing and screening round. Results and limitationsOverall, 7625 men had at least one PSA test and 1022 men were diagnosed with PC. For men with screen-detected PC, age was associated with the risk of clinically significant PC above and beyond screening round and year of testing (p < 0.001). For each 1-yr increase in age, the risk of being diagnosed with a Gleason score ≥3 + 4 cancer (vs <7) increased by 11% (95% confidence interval [CI] 4.7–17), whereas the risk of being diagnosed with a Gleason score ≥4 + 3 cancer (vs <7) increased by 8.5% (95% CI –1.6 to 20). ConclusionsThe increased risk of a higher Gleason score in older men should be considered when counseling men regarding early diagnosis and treatment for PC. Patient summaryWe found that older age increased both the risk of prostate cancer and the risk of more aggressive prostate cancer.

Household Contact Tracing With Intensified Tuberculosis and Human Immunodeficiency Virus Screening in South Africa: A Cluster-Randomized Trial.

BackgroundHousehold contact tracing for tuberculosis (TB) may facilitate diagnosis and access to TB preventive treatment (TPT). We investigated whether household contact tracing and intensive TB/human immunodeficiency virus (HIV) screening would improve TB-free survival.MethodsHousehold contacts of index TB patients in 2 South African provinces were randomized to home tracing and intensive HIV/TB screening or standard of care (SOC; clinic referral letters). The primary outcome was incident TB or death at 15 months. Secondary outcomes included tuberculin skin test (TST) positivity in children ≤14 years and undiagnosed HIV.ResultsFrom December 2016 through March 2019, 1032 index patients (4459 contacts) and 1030 (4129 contacts) were randomized to the intervention and SOC arms. Of intervention arm contacts, 3.2% (69 of 2166) had prevalent microbiologically confirmed TB. At 15 months, the cumulative incidence of TB or death did not differ between the intensive screening (93 of 3230, 2.9%) and SOC (80 of 2600, 3.1%) arms (hazard ratio, 0.90; 95% confidence interval [CI], .66–1.24). TST positivity was higher in the intensive screening arm (38 of 845, 4.5%) compared with the SOC arm (15 of 800, 1.9%; odds ratio, 2.25; 95% CI, 1.07–4.72). Undiagnosed HIV was similar between arms (41 of 3185, 1.3% vs 32 of 2543, 1.3%; odds ratio, 1.02; 95% CI, .64–1.64).ConclusionsHousehold contact tracing with intensive screening and referral did not reduce incident TB or death. Providing referral letters to household contacts of index patients is an alternative strategy to home visits.Clinical Trials RegistrationISRCTN16006202.

Abstract 12176: Oral Anticoagulant Therapy Following Single-Lead ECG Screening Among Older Patients With Atrial Fibrillation: The VITAL-AF Trial

Introduction: A substantial proportion of patients with atrial fibrillation do not take oral anticoagulants (OAC). Point of care ECG testing at primary care visits may prompt reassessment of OAC eligibility in patients with AF. Methods: VITAL-AF (NCT035115057) was a cluster-randomized trial of AF screening using single-lead handheld electrocardiograms within 16 primary care practices affiliated with Massachusetts General Hospital. The goal of VITAL-AF was to screen for undiagnosed AF. For pragmatic reasons the trial included all individuals aged ≥ 65 years, including those with an established diagnosis of AF. We evaluated screening uptake among prevalent AF patients in the screening arm, OAC initiation among both screening and control patients with prevalent AF, and OAC initiation by screening result (adjusted for stroke/bleed risk factors compared to all patients not screened). OAC use was identified using electronic health record medication lists during the 1-year prior to and following a patient’s study index visit. Results: Prevalent AF was present in 2,250 patients (75% on OAC) in the screening arm and 2,343 patients (76% on OAC) in the control arm. 90% of patients in the screening arm were screened at least once during the study period (mean 2.4 times screened). 31.5% had a “Possible AF” and 17.2% had an “Unclassified” automated algorithm screening result during their first screening encounter (40.1% “Possible AF” and 27.4% “Unclassified” during any encounter). Overall, OAC initiation was similar among prevalent AF patients from the screening arm and control arm ( Table ). OAC initiation was higher among screened patients who had a “Possible AF” automated result (Adjusted Odds Ratio 1.14, 95% CI: 1.05-1.24). Conclusions: Point of care cardiac rhythm assessment was not associated with significant changes in the use of OAC in patients with a history of AF. However, screened patients not on OAC who had a positive single-lead ECG were more likely to initiate OAC.

Intervention-related Deaths in the European Randomized Study of Screening for Prostate Cancer

BackgroundIdentification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. ObjectiveTo investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). Design, setting, and participantsERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55–69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. Outcome measurements and statistical analysisCauses of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. Results and limitationsIn total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99–1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. ConclusionsIntervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. Patient summaryWe investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified.

Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis.

BackgroundThe NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial.MethodsFrom October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50–75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence.Findings1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1–7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41–1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76–0.92) from nine eligible trials.InterpretationThe UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups.FundingNIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.

Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis.

Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD). In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon. DCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment. clinicaltrials.gov NCT03519425.

PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

Instrumental variable estimation of early treatment effect in randomized screening trials.

The primary analysis of randomized screening trials for cancer typically adheres to the intention-to-screen principle, measuring cancer-specific mortality reductions between screening and control arms. These mortality reductions result from a combination of the screening regimen, screening technology and the effect of the early, screening-induced, treatment. This motivates addressing these different aspects separately. Here we are interested in the causal effect of early versus delayed treatments on cancer mortality among the screening-detectable subgroup, which under certain assumptions is estimable from conventional randomized screening trial using instrumental variable type methods. To define the causal effect of interest, we formulate a simplified structural multi-state model for screening trials, based on a hypothetical intervention trial where screening detected individuals would be randomized into early versus delayed treatments. The cancer-specific mortality reductions after screening detection are quantified by a cause-specific hazard ratio. For this, we propose two estimators, based on an estimating equation and a likelihood expression. The methods extend existing instrumental variable methods for time-to-event and competing risks outcomes to time-dependent intermediate variables. Using the multi-state model as the basis of a data generating mechanism, we investigate the performance of the new estimators through simulation studies. In addition, we illustrate the proposed method in the context of CT screening for lung cancer using the US National Lung Screening Trial data.

Bispecific Antibodies with Native Human IgG Structure As Mimetics for FVIII Activity

Background: Non-factor therapies for hemophilia A are being evaluated to overcome the need for frequent i.v. administration and address therapeutic issues caused by anti-FVIII inhibitors. One possibility to substitute the lack of FVIII activity is the development of a bispecific antibody (biAb) that targets the two coagulation factors FIXa and FX. The two arms' binding characteristics and relative orientation are thought to be important to optimally bridge FIXa and FX and to at least partially mimic the function of FVIIIa, and facilitate FXa generation.Aim: To identify biAbs targeting FIXa and FX that have FVIII-mimetic activity using the κλ body platform, generating biAbs that are indistinguishable from native human IgG. As hemophilia A patients require life-long treatment, a native human IgG structure represents an advantage for the chronic treatment of this patient population.Methods: We used the κλ body platform to identify novel biAbs with FVIII-mimetic activity. First, antibodies against different forms of FIX(a) and FX(a) were selected using phage display. Then, κλ bodies were produced by co-expressing a common heavy chain and two light chains. As the κλ body is the major form secreted in the supernatant of the transfected cells, conveniently, cell culture supernatants were used directly for functional screening and multiple arms optimized in parallel.Results: Over 1000 unique antibodies were identified that target different epitopes on each factor, allowing for the generation of thousands of different biAbs combinations. To date, over 10,000 biAbs have been functionally screened. Unlike previous studies which only rarely identified FVIII-mimetic biAbs (Sampei et al., PLoS One 2013), the present approach resulted in isolation of ~350 unique arm combinations showing considerable FVIII mimetic activity. These results suggest that multiple geometries of the FIXa/FX biAb complex can lead to FVIII-mimetic activity.Conclusion: Theκλ body technology is optimal for generating native human and non-engineered biAbs of high epitope diversity, and exploring a wide range of geometries which is crucial to obtain biAbs for efficient FX activation. Efficient expression supernatant screening allowed multiple arms to be optimized in parallel and significantly improved FVIII-mimetic activity. The native human IgG structure of the FVIII-mimetic κλ bodies make them ideal candidates for long-term treatment of hemophilia A. DisclosuresKnappe:Shire: Employment. Fischer:GLG (Gerson Lehrman Group): Consultancy; Novimmune: Employment, Equity Ownership, Patents & Royalties, Research Funding. Douillard:Shire: Employment. Hartmann:Shire: Employment. Schrenk:Shire: Employment. Ravn:NovImmune: Employment, Equity Ownership. Magistrelli:Pierre Fabre: Patents & Royalties; NovImmune SA: Employment, Equity Ownership, Patents & Royalties. Gueneau:Novimmune: Employment, Equity Ownership. Didelot:Novimmune: Employment. Masternak:Novimmune: Employment, Equity Ownership. Kosco-Vilbois:Novimmune SA: Employment, Equity Ownership. Scheiflinger:Shire: Employment, Equity Ownership; Baxter: Equity Ownership. Dockal:Shire: Employment, Equity Ownership; Baxter: Equity Ownership, Patents & Royalties; Baxalta: Patents & Royalties.

Neuroblastoma Screening at 1 Year of Age: The Final Results of a Controlled Trial.

BackgroundNeuroblastoma screening aims to reduce neuroblastoma-related mortality. A controlled trial showed no reduction in stage 4 disease incidence and preliminary mortality data. This article presents epidemiologic and clinical data 20 years after cessation of the screening program.MethodsThe patients with detected disease in the screening area were compared with the clinically diagnosed patients in the control area and in the prestudy and poststudy cohorts. All statistical tests were 2-sided.ResultsThe cumulative incidence for children aged 1 to 6 years in the birth study cohorts (1994-1999) in the screening arm was 13.4 cases per 100 000 births (95% confidence interval [CI] = 12.2 to 14.6) based on 61.2% of screening participants and 38.8% of nonparticipants. Screening participants had a cumulative incidence of 15.7 (95% CI = 14.0 to 17.4) per 100 000 births. The cumulative incidence in the contemporary control cohort was 9.3 (95% CI = 8.2 to 10.3) per 100 000 births, 7.6 (95% CI = 6.8 to 8.4) in the prestudy cohort, and 8.1 (95% CI = 7.4 to 8.9) in the poststudy cohort from 2000 to 2004 (P < .001 each). The increased incidence in the screening cohort was restricted to stages 1 through 3, while stage 4 incidence was not reduced. The cumulative mortality for deaths within 10 years from diagnosis and per 100 000 births remained unchanged. Patients with stage 4 disease detected by screening had better biological characteristics and an improved outcome compared with those stage 4 cases not detected by screening.ConclusionsNeuroblastoma screening at 1 year of age reduced neither stage 4 incidence nor neuroblastoma mortality and was affected by overdiagnosis, leading to unnecessary treatment. A few screening-detected stage 4 cases represent a biologically interesting subgroup but do not change the recommendation to close the “catecholamine-based neuroblastoma screening book.”

Outcomes of prostate cancer screening among men using antidiabetic medication

Diabetic men have decreased risk for prostate cancer (PCa) overall and lower PSA compared to non-diabetics. This may affect the outcomes of PSA-based screening. We investigated the effect of PSA-based screening at 4-year intervals on PCa incidence and mortality separately among users and non-users of antidiabetic medication with the hypothesis that screening would detect less low-grade cancer and more high-grade cancer in diabetic men. A cohort of 80,458 men from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to national prescription database to obtain information on antidiabetic medication purchases. PCa risk and mortality were compared between the FinRSPC screening arm (SA) and the control arm (CA) separately among users and non-users of antidiabetic medication. Among antidiabetic medication users median PSA was lower than in non-users (0.93 and 1.09 ng/ml, respectively, P for difference = 0.001). Screening increased overall PCa incidence compared to CA after the first screen both among medication users and non-users (HR 1.31, 95% CI 1.08–1.60 and HR 1.55, 95% CI 1.44–1.66, respectively). On the second and third screen the difference between SA and CA attenuated only among medication users. Detection of Gleason 6 tumors was lower among medication users, whereas no difference was observed in detection of Gleason 8–10 cancers. Concordantly, screening affected PCa mortality similarly regardless of antidiabetic medication use (HR 0.38, 95% CI 0.14–1.07 and HR 0.19, 95% CI 0.11–0.33 among users and non-users after three screens, respectively. P for difference = 0.18). Median PSA is lower in men using antidiabetic drugs than among non-users. Systematic PSA screening detects less low-risk tumors among medication users, whereas detection of high-risk tumors and mortality effects are similar regardless of medication use. This suggests that antidiabetic medication users may form a suitable target group for PCa screening, with less screening-related overdiagnosis of indolent tumors.

Estimation of overdiagnosis in colorectal cancer screening with sigmoidoscopy and faecal occult blood testing: comparison of simulation models

ObjectiveTo estimate overdiagnosis of colorectal cancer (CRC) for screening with sigmoidoscopy and faecal occult blood testing (FOBT).DesignSimulation study using data from randomised trials.SettingPrimary screening, UK, NorwayParticipants152 850 individuals from the...

Effect of screening by clinical breast examination on breast cancer incidence and mortality after 20 years: prospective, cluster randomised controlled trial in Mumbai

ObjectiveTo test the efficacy of screening by clinical breast examination in downstaging breast cancer at diagnosis and in reducing mortality from the disease, when compared with no screening.DesignProspective, cluster randomised...

Abstract OT-22-01: Opportunities and lessons learned in using electronic health record patient portal (MyChart) for recruitment to the population-based WISDOM study

Abstract Background: WISDOM is a preference-tolerant, pragmatic study comparing annual mammogram screening to personalized, risk-based breast screening in healthy women with a target accrual of 100,000. This sizable recruitment goal requires creative and broad-based strategies that are not typical for traditional clinical research. One of the recruitment methods is use of an electronic health record patient portal (Epic’s MyChart) to invite patients to participate in research. We tested various MyChart implementation strategies across WISDOM recruitment sites and report response rates, barriers and lessons learned. The study is registered on ClinicalTrials.gov, NCT02620852. Methods: Women aged 40-74 years with no history of breast cancer, DCIS, or double mastectomy can join the WISDOM Study online at wisdomstudy.org. Participants either elect to be randomized or self-select one of the study arms, the control (annual mammogram screening) arm or the treatment (personalized, risk-based breast screening) arm. All study steps can be completed electronically, with no requirement to travel to a study site. University of California, Los Angeles (UCLA) was the first WISDOM site to gain approval to use MyChart as a recruitment tool as part of the Clinical Translational Science Institute pilot in Spring 2018. The pilot was designed to demonstrate feasibility, patient response, and recruitment metrics. Following UCLA’s pilot, additional WISDOM sites received approval to use MyChart; however, implementation differed across sites based on local medical center leadership decisions. MyChart Implementation: As of July 2020, use of MyChart is ongoing at five of WISDOM’s six initial recruitment sites (UCLA, Sanford Health, UCSF, UCSD, UCI). Three sites (UCLA, Stanford, and UCSF) implemented MyChart broadly, and two sites (UCI and UCSD) are phasing in MyChart recruitment. UCLA and Sanford Health implemented MyChart recruitment through a centralized approach targeting all eligible patients and sending a MyChart invitation with a link to the study’s enrollment website. UCSF was approved to send WISDOM information on the MyChart portal, but the patients must opt in to learn more by outreach from a research coordinator. UCSD and UCI approaches are more limited requiring departmental or primary care provider approval for communications to be sent to patients. Results: MyChart enabled direct communication to a large number of potential study participants at UCLA and Sanford Health (UCLA 107,829, Sanford Health 86,684) during a 12-month period. The experiences of both sites were similar in that 50% of individuals read the MyChart message, 2.5-5% registered for additional information, and 1.5-2.5% consented to participate. UCSF’s implementation approach was similar with 8005 individuals invited, 6.6% indicating interest to participate, and 2.4% consenting. Although the number of consented participants represented a small portion of the total women consented to join the study to date, the recruitment rates from using MyChart were 2.5-10X higher compared to sites that did not use it or were in pilot phase. Participating sites saw 30%-50% increased recruitment rates during periods when MyChart messages were in use. Implementations at the departmental (UCSD) and primary care provider level (UCI) demonstrated similar trends (3.8% and 3% consented respectively), albeit with smaller samples. Conclusions: Use of electronic health record patient portal (MyChart) recruitment for the WISDOM Study increased enrollment rate by site and is a cost-effective approach to recruiting for large scale trials with broad eligibility criteria like the WISDOM Study. Citation Format: Antonio Petruse, Alyssa Rocha, Liliana Johansen, Neil Wenger, Mandy Che, Steele Fors, Hannah L Park, Janet Wernisch, Irene Acerbi, Allison S Fiscalini, Jasmin Hassam, Andrea LaCroix, Barbara Parker, Lisa Madlensky, Laura Van't Veer, Celia Kaplan, Hoda Anton-Culver, Andrea Kaster, Skye Stewart, Samrrah Rouf, Alexander Borowsky, Ian Hurley, Robert Hiatt, Vivian Lee, Diane Heditsian, Susie Brain, Olufunmilayo Olopade, Deepa Sheth, Laura Esserman, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, Arash Naeim. Opportunities and lessons learned in using electronic health record patient portal (MyChart) for recruitment to the population-based WISDOM study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-22-01.

The next generation of collaborative care: The design of a novel web-based stepped collaborative care intervention delivered via telemedicine for people diagnosed with cancer

BackgroundThe NIH consensus statement on cancer-related symptoms concluded the most common and debilitating were depression, pain and fatigue [1–6]. Although the comorbidity of these symptoms is well known and may have similar underlying biological mechanisms no intervention has been developed to reduce these symptoms concurrently. The novel web-based stepped collaborative care intervention delivered by telemedicine is the first to be tested in people diagnosed with cancer. MethodsWe plan to test a web-based stepped collaborative care intervention with 450 cancer patients and 200 caregivers in the context of a randomized controlled trial. The primary endpoint is quality of life with other primary outcomes including patient-reported depression, pain, fatigue. Secondary outcomes include patient serum levels of pro-inflammatory cytokines and disease progression. We also will assess informal caregiver stress, depression, and metabolic abnormalities to determine if improvements in patients' symptoms also relate to improvement in caregiver outcomes. ResultsThe trial is ongoing and a total of 382 patients have been randomized. Preliminary analyses of the screening tools used for study entry suggest that Center for Epidemiological Studies-Depression (CESD) scale has good sensitivity and specificity (0.81 and 0.813) whereas the scale used to assess pain (0.47 and 0.91) and fatigue (0.11 and 0.91) had poor sensitivity but excellent specificity. Using the AUROC, the best cut point for the CES-D was 19, for pain was 4.5; and for fatigue was 2.5. Outcomes not originally proposed included health care utilization and healthcare charges. The first 100 patients who have been followed a year post-treatment, and who were less than 75 years and randomized to the web-based stepped collaborative care intervention, had lower rates of complications after surgery [χ2 = 5.45, p = 0.02]. For patients who survived 6 months or less and were randomized to the web-based stepped collaborative care intervention, had lower rates of 90-day readmissions when compared to patients randomized to the screening and referral arm [χ2 = 4.0, p = 0.046]. Patients randomized to the collaborative care intervention arm had lower overall health care activity-based costs of $16,758 per patient per year when compared to the screening and referral arm. DiscussionThis novel web-based stepped stepped collaborative care intervention, delivered via telemedicine, is expected to provide a new strategy to improve the quality of life in those diagnosed with cancer and their caregivers. Trial registrationClinicalTrials.govNCT02939755

Major failings of trial procedures and quality of screening fatally compromise the results of the Canadian National Breast Screening Studies

Despite overwhelming evidence of a major reduction in deaths, the debate about the efficacy of breast cancer screening has continued for over 50 years. The poor results in the Canadian National Breast Screening Studies (CNBSS) have been used to challenge the benefits shown by the other randomized, controlled trials. They continue to be used in assessing the value of breast cancer screening despite their unblinded allocation process, which first identified women with breast abnormalities and then assigned them on open lists allowing for nonrandom assignment, compromising the trials and rendering their results unreliable. There were, statistically significantly, more women with advanced cancers who were assigned to the screening arm in CNBSS1. The early results for CNBSS1 showed an excess of women dying in the screening arm, and an (otherwise inexplicable) greater than 90%, 5-year survival for the control women. The failure of random assignment also explains why the clinically evident cancers were larger in the screening arms than the cancers in the "usual care" arms, despite the fact that the screened women underwent very intense clinical breast examinations each year by highly skilled examiners. The claim that balanced demographic factors prove random assignment is also false. Nonrandom allocation of a hundred or more women with clinically evident abnormalities would have no detectable influence on the distribution of demographic factors. In summary, policy decisions about mammography should not be influenced by the results of the CNBSS.