Screening Arm Research Articles

B-308 Analytical and clinical performance of a novel ovarian cancer screening test in asymptomatic women

Abstract Background Ovarian cancer (OC) ranks among the deadliest gynecological cancers, often diagnosed at advanced stages when treatment options are limited. Costly sequencing methods and established immunoassay and imaging-based methods lack early-stage sensitivity, highlighting the need for a cost-effective test with improved performance. Extracellular vesicles (EVs) produced in abundance by all cells can potentially improve test sensitivity and detection of multiple colocalized cancer specific markers can improve test specificity. The randomized controlled trial UKCTOCS (United Kingdom Collaborative Trial of Ovarian Cancer Screening) where over 200,000 postmenopausal asymptomatic women were randomly assigned to three arms revealed no significant reduction in mortality with OC screening. We report on an EV-based OC Test performance in serum samples from asymptomatic postmenopausal women in UKCTOCS. Methods The OC Test was previously locked (biomarkers, method, cutoff) and validated in an independent cohort. We evaluated the OC Test in a blinded case-control study nested within the no screening (NS) and annual ultrasound screening (USS) arms of UKCTOCS. All UKCTOCS participants provided a blood sample at study entry. Cases were all women who developed high grade serous ovarian cancer (HGSOC) within 36 months following sample donation (spun within 28 hours). They were matched by age at collection (+/-2 years) to women who had no OC detected either before or within the trial follow up period (controls). Where a case had >1 sample within the 0-36 months period, the control sample was matched to the case sample closest to diagnosis. The OC Test was run with a locked method and classifier algorithm utilizing 3 independent biomarker combinations tested in duplicate. OC Test results were calculated based on a previously determined cutoff prior to unblinding of clinical outcomes. Run controls were prepared by harvesting conditioned media from COV413A cell cultures (an ovarian epithelial-serous carcinoma cell line), purifying EVs and spiking into pre-screened OC Test negative human plasma at three levels. Run controls were run twice per day, one replicate per run for 17 days. Results We retrospectively assessed 116 samples from 108 cases (63 clinical Dx NS, 15 clinical Dx USS, 30 screen detected USS) women with HGSOC and 1310 samples from 1310 controls. OC test sensitivity for HGSOC was 84% (36/43; 95% CI 69%-93%), Stage I/II sensitivity was 89% (8/9; 95% CI 51%-99%) and the AUC (area under the curve) was 0.93 for case samples drawn 0-12 months prior to clinical Dx and all control samples. The OC Test specificity was 98% (1099/1176, 95% CI 97%-98%). Within laboratory CVs were 20.9%, 12.7% and 0.6% for low negative, high negative and high positive run controls respectively. Data from 143 samples (10%, 9 cases, 134 controls) were excluded due to operator error, low sample volume or quality issues. Conclusions The OC Test is capable of highly sensitive detection of HGSOC within one year of clinical diagnosis including at the earliest stages of disease while maintaining exceptionally high specificity. The results demonstrate the potential application of the OC Test for ovarian cancer screening in asymptomatic women.

Cost effectiveness of esophageal varices screening strategies of cirrhotic patients with portal hypertension

ObjectivesIn France, screening for esophageal varices (EVs) in cirrhotic patients with portal hypertension (PH) is performed by esophagogastroduodenoscopy (EGD). Though proven effective, EGD screening may be unpleasant for some patients. Our study sought to compare the cost-effectiveness of PillCam (Medtronic, Minneapolis, USA) esophageal capsule endoscopy (ECE), a less invasive test, versus EGD, for EV screening, from the perspective of the French national health system (NHS). In secondary objectives we compared the cost-effectiveness of ECE versus no screening for patients not compliant with EGD screening, and the cost-effectiveness of a screening strategy (ECE or EGD) versus no screening strategy at all. MethodsWe constructed a Markov model with data from the literature, applying it to two simulated cohorts of adult patients with cirrhosis and PH not previously screened for EVs. These patients were divided into EGD and ECE screening arms and tracked over a virtual 10-year period. Cost-effectiveness was defined as cost (in euros) per quality-adjusted life year (QALY). ResultsIn the base-case analysis, ECE is more expensive than EGD (€3,606 vs. €3,030) and less effective by 0.0098 QALY (5.2099 vs. 5.2197 QALYs). Probabilistic sensitivity analysis shows that ECE has only a 2.1% probability of being cost-effective at willingness-to-pay (WTP) of €30,000/QALY. ConclusionsAlthough patient compliance is apparently higher with ECE, it is not cost-effective at a WTP of €30,000/QALY and should not be considered in all patients with PH. Its cost-effectiveness should be reevaluated in the event of patient refusal of EGD follow-up. Public Interest SummaryEsophagogastroduodenoscopy (EGD) is gold standard to screen cirrhotic patients with portal hypertension for esophageal varices, but its unpleasantness lowers compliance. We evaluated the cost-effectiveness of a more acceptable alternative for patients: the esophageal capsule endoscopy (ECE).Our results show that screening by ECE is more expensive and less effective than by EGD from the perspective of the French national health system. It cannot be used as an alternative for all patients suffering from PH in France. Further investigations could be conducted to assess the effectiveness of ECE for the sub population of patients with PH who are totally refractory to EGD and may suffer from inadequate follow-up due to lack of screening.

Echocardiographic screening for heart failure and optimization of the care pathway for individuals with pacemakers: a randomized controlled trial.

Individuals with pacemakers are at increased risk of left ventricular systolic dysfunction (LVSD). Whether screening for and optimizing the medical management of LVSD in these individuals can improve clinical outcomes is unknown. In the present study, in a multicenter controlled trial (OPT-PACE), we randomized 1,201 patients (717 men) with a pacemaker to echocardiography screening or usual care. In the screening arm, LVSD was detected in 201 of 600 (34%) patients, who then received management in either primary care or a specialist heart failure (HF) and devices clinic. The primary outcome of the trial was the difference in a composite of time to first HF hospitalization or death. Over 31 months (interquartile range = 30-40 months), the primary outcome occurred in 106 of 600 (18%) patients receiving echocardiography screening, which was not significantly different compared with the occurrence of the primary outcome in 115 of 601 (19%) patients receiving the usual care (hazard ratio = 0.89; 95% confidence interval = 0.69, 1.17). In a prespecified, nonrandomized, exploratory analysis, patients with LVSD managed by the specialist clinic experienced the primary outcome event less frequently than those managed in primary care. The results of this trial indicate that echocardiography screening commonly identifies LVSD in individuals with pacemakers but alone does not alter outcomes. ClinicalTrials.gov registration: NCT01819662 .

Atrial Fibrillation Burden on a 14-Day ECG Monitor: Findings From the GUARD-AF Trial Screening Arm

BackgroundThe “burden” of atrial fibrillation (AF) detected by screening likely influences stroke risk, but the distribution of burden is not well described. ObjectivesThis study aims to determine the frequency of AF and the distribution of AF burden found when screening individuals ≥70 years of age with a 14-day electrocardiograph monitor. MethodsThis is a cohort study of the screening arm of a randomized AF screening trial among those ≥70 years of age without a prior AF diagnosis (between 2019 and 2021). Screening was performed with a 14-day continuous electrocardiogram patch monitor. ResultsAnalyzable patches were returned by 5,684 (95%) of screening arm participants; the median age was 75 years (Q1-Q3: 72-78 years), 57% were female, and the median CHA2DS2-VASc score was 3 (Q1-Q3: 2-4). AF was detected in 252 participants (4.4%); 29 (0.5%) patients had continuous AF and 223 (3.9%) had paroxysmal AF. Among those with paroxysmal AF, the average indices of AF burden were of low magnitude with right-skewed distributions. The median percent time in AF was 0.46% (Q1-Q3: 0.02%-2.48%), or 75 (Q1-Q3: 3-454) minutes, and the median longest episode was 38 (Q1-Q3: 2-245) minutes. The upper quartile threshold of 2.48% time in AF corresponded to 7.6 hours. Age greater than 80 years was associated with screen-detected AF in our multivariable model (OR: 1.46; 95% CI: 1.06-2.02). ConclusionsMost AF detected in these older patients was very low burden. However, one-quarter of those with AF had multiple hours of AF, raising concern about stroke risk. These findings have implications for targeting populations for AF screening trials and for responding to heart rhythm alerts from mobile devices (GUARD-AF [A Study to Determine if Identification of Undiagnosed Atrial Fibrillation in People at least 70 Years of Age Reduces the Risk of Stroke]; NCT04126486)

Applying behavioural economics principles to increase demand for free HIV testing services at private doctor-led clinics in Johannesburg, South Africa: A randomised controlled trial.

Expanding free HIV testing service (HTS) access to include private clinics could increase testing rates. A donor funded programme, GP Care Cell, offered free HIV testing at selected private doctor-led clinics but uptake was low. We investigated whether HTS demand creation materials that used behavioural economics principles could increase demand for HIV testing at these clinics. We conducted a randomised controlled trial in Johannesburg, South Africa (January-April 2022) distributing brochures promoting HTS to adults in five private doctor-led clinic catchment areas. Individuals were randomised to receive three brochure types: (1) "Standard of care" (SOC) advertising a free HIV test and ART; (2) "Healthy lifestyle screening" promoted free low-cost health screenings in addition to HTS; and (3) "Recipient of care voucher" leveraged loss aversion and the endowment effect by highlighting the monetary value of free HTS. The primary outcome was presenting at the clinic following exposure to the brochures. Logistic regression compared outcomes between arms. We found that of the 12,129 brochures distributed, 658 were excluded because of errors or duplicates and 11,471 were analysed. About 59% of brochure recipients were male and 50,3% were aged 25-34 years. In total, 448 (3.9%) brochure recipients presented at the private doctor-led clinics of which 50.7% were males. There were no significant differences in clinic presentation between the healthy lifestyle screening and SOC arm (Adjusted Odds Ratio [AOR] 1.02; 95% CI 0.79-1.32), and similarly between the recipient of care voucher and SOC arm (AOR 1.08; 95% CI 0.84-1.39). Individuals were more likely to attend centrally-located clinics that had visible HTS branding (AOR = 5.30; 95% CI: 4.14-6.79). Brochures that used behavioural insights did not increase demand for HTS at private doctor-led clinics. However, consistent distribution of the brochures may have potential to increase HIV testing uptake at highly visible private doctor-led clinics.

Estimating sojourn time and sensitivity of screening for ovarian cancer using a Bayesian framework.

Ovarian cancer is among the leading causes of gynecologic cancer-related death. Past ovarian cancer screening trials using combination of cancer antigen 125 testing and transvaginal ultrasound failed to yield statistically significant mortality reduction. Estimates of ovarian cancer sojourn time-that is, the period from when the cancer is first screen detectable until clinical detection-may inform future screening programs. We modeled ovarian cancer progression as a continuous time Markov chain and estimated screening modality-specific sojourn time and sensitivity using a Bayesian approach. Model inputs were derived from the screening arms (multimodal and ultrasound) of the UK Collaborative Trial of Ovarian Cancer Screening and the Prostate, Lung, Colorectal and Ovarian cancer screening trials. We assessed the quality of our estimates by using the posterior predictive P value. We derived histology-specific sojourn times by adjusting the overall sojourn time based on the corresponding histology-specific survival from the Surveillance, Epidemiology, and End Results Program. The overall ovarian cancer sojourn time was 2.1 years (posterior predictive P value = .469) in the Prostate, Lung, Colorectal and Ovarian studies, with 65.7% screening sensitivity. The sojourn time was 2.0 years (posterior predictive P value = .532) in the United Kingdom Collaborative Trial of Ovarian Cancer Screening's multimodal screening arm and 2.4 years (posterior predictive P value = .640) in the ultrasound screening arm, with sensitivities of 93.2% and 64.5%, respectively. Stage-specific screening sensitivities in the Prostate, Lung, Colorectal and Ovarian studies were 39.1% and 82.9% for early-stage and advanced-stage disease, respectively. The histology-specific sojourn times ranged from 0.8 to 1.8 years for type II ovarian cancer and 2.9 to 6.6 years for type I ovarian cancer. Annual screening is not effective for all ovarian cancer subtypes. Screening sensitivity for early-stage ovarian cancers is not sufficient for substantial mortality reduction.

Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: inequities in diagnostic yield.

Socioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on inequities in health gain remain unclear. Sixty-year-olds were randomly recruited from the Swedish population between March 2014 and March 2020 and invited to undergo either 2 rounds of fecal immunochemical testing (FIT) 2 years apart (n = 60 137) or primary colonoscopy just once (n = 30 400). By linkage to Statistics Sweden's registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia in each screening arm (intention-to-screen analysis). In the biennial FIT arm, we predicted the probability of exceeding the yield in the primary colonoscopy arm by linear extrapolation of the cumulative yield to (hypothetical) additional rounds of FIT. In the lowest income group, the yield of advanced neoplasia was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after 2 rounds of FIT vs 1.93% (95% CI = 1.49% to 2.40%) in the primary colonoscopy arm. Extrapolation to a third round of FIT implied a 86% probability of exceeding the yield in the primary colonoscopy arm. In the highest income group, we found a more pronounced yield gap between the 2 screening strategies-2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%)- implying a low (2%) predicted probability of exceeding yield after a third round of FIT. Yield of advanced neoplasia from 2 rounds of FIT 2 years apart was poorer as compared with primary colonoscopy, but the difference was less in lower socioeconomic groups. ClinicalTrials.gov identifier NCT02078804.

Cost effectiveness of colorectal cancer screening in the Dominican Republic.

e23033 Background: Colorectal cancer (CRC) incidence in the Dominican Republic (DR) is increasing, and CRC now ranks as the third-most prevalent cancer in the DR. There are no national CRC screening guidelines in the DR, and CRC screening is not routinely performed. We evaluated the impact of nationwide CRC screening by comparing the cost-effectiveness of four CRC screening strategies to the current practice of no screening. Methods: We developed a Markov model comparing four CRC screening strategies to the current practice of no screening, or natural history (NH): colonoscopy every ten years (Colo); sigmoidoscopy every five years (Sig); fecal immunochemical test biennially (FIT); and fecal occult blood test biennially (FOBT). Model inputs for screening arms were derived from international randomized controlled trials whenever possible. Data from The Rosa Emilia Sánchez Pérez de Tavares National Cancer Institute in the DR was used to estimate baseline CRC incidence, stage distribution and mortality. Screening was implemented from age 45 to 75. We assumed a 60.6% adherence rate for each screening arm. The model was cross validated by comparing the estimated lifetime impact of each screening arm on CRC incidence and mortality to estimates derived from the MIcrosimulation SCreening Analysis (MISCAN) Colorectal Cancer Model in the US. The primary outcome was the incremental cost-effectiveness ratio (ICER) of each screening strategy. Secondary outcomes included life expectancy, total cost, CRC incidence and CRC-related mortality. The willingness to pay threshold (WTP) was set to the 2022 DR gross domestic product per person ($10,111.20/life year gained). Results: In the NH strategy, 2.3% of the population developed CRC, and 1.2% died from CRC, with a lifetime cost of 203.47 per person. Compared to NH, FIT prevented 27% of CRCs and 37% of CRC deaths, with a lifetime cost of 244.76 per person. Colo was more effective than FIT, preventing 33% and 43% of CRC cases and deaths, respectively, compared to NH. However, the ICER for Colo exceeded the WTP threshold. One-way sensitivity analyses showed that the model is most sensitive to test performance characteristics and test costs. Conclusions: Among the evaluated CRC screening strategies, FIT is the cost-effective option, averting a significant number of CRC cases and deaths, at an incremental cost that is well within the WTP threshold for the DR. Inclusion of local data on the effectiveness and acceptability of the tested CRC screening modalities would improve this model, and strengthen the credibility of our findings. [Table: see text]

Sociodemographic characteristics associated with cervical cancer screening participation by send-to-all and opt-in HPV self-sampling: Who benefits? Results from a randomized controlled trial among long-term non-attending women in Norway.

With the objective to investigate associations between sociodemographic characteristics and participation in interventions designed to increase participation in cervical cancer screening among under-screened women, we randomized a random sample of 6000 women in Norway aged 35-69 years who had not attended cervical screening for ≥10 years to receive either (i) a reminder to attend regular screening (control), (ii) an offer to order a self-sampling kit (opt-in), or (iii) a self-sampling kit unsolicited (send-to-all). We analyzed how sociodemographic characteristics were associated with screening participation within and between screening arms. In the send-to-all arm, increased screening participation ranged from 17.1% (95% confidence interval [95% CI] = 10.3% to 23.8%) to 30.0% (95% CI = 21.5% to 38.6%) between sociodemographic groups. In the opt-in arm, we observed smaller, and at times, non-significant increases within the range 0.7% (95% CI = -5.8% to 7.3%) to 19.1% (95% CI = 11.6% to 26.7%). In send-to-all versus control comparisons, there was greater increase in participation for women in the workforce versus not (6.1%, 95% CI = 1.6% to 10.6%), with higher versus lower income (7.6%, 95% CI = 2.2% to 13.1%), and with university versus primary education (8.5%, 95% CI = 2.4% to 14.6%). In opt-in versus control comparisons, there was greater increase in participation for women in the workforce versus not (4.6%, 95% CI = 0.7% to 8.5%), with higher versus lower income (6.3%, 95% CI = 1.5% to 11.1%), but lower increase for Eastern European versus Norwegian background (-12.7%, 95% CI = -19.7% to -5.7%). Self-sampling increased cervical screening participation across all sociodemographic levels, but inequalities in participation should be considered when introducing self-sampling, especially with the goal to reach long-term non-attending women.

Which men benefit from prostate cancer screening? Prostate cancer mortality by subgroup in the European Randomised Study of Screening for Prostate Cancer.

To evaluate whether a subgroup of men can be identified that would benefit more from screening than others. This retrospective cohort study was based on three European Randomised Study of Screening for Prostate Cancer (ERSPC) centres, Finland, the Netherlands and Sweden. We identified 126 827 men aged 55-69 years in the study who were followed for maximum of 16 years after randomisation. The primary outcome was prostate cancer (PCa) mortality. We analysed three age groups 55-59, 60-64 and 65-69 years and PCa cases within four European Association of Urology (EAU) risk groups: low, intermediate, high risk, and advanced disease. The hazard ratio (HR) for PCa mortality in the screening arm relative to the control arm for men aged 55-59 years was 0.96 (95% confidence interval [CI] 0.75-1.24) in Finland, 0.70 (95% CI 0.44-1.12) in the Netherlands and 0.42 (95% CI 0.24-0.73) in Sweden. The HR for men aged 60-64 years was 1.03 (95% CI 0.77-1.37) in Finland, 0.76 (95% CI 0.50-1.16) in the Netherlands and 0.97 (95% CI 0.64-1.48) in Sweden. The HR for men aged 65-69 years was 0.80 (95% CI 0.62-1.03) in Finland and 0.57 (95% CI 0.38-0.83) in the Netherlands, and this age group was absent in Sweden. In the EAU risk group analysis, PCa mortality rates were materially lower for men with advanced disease at diagnosis in all three countries: 0.67 (95% CI 0.56-0.82) in Finland, 0.28 (95% CI 0.18-0.44) in the Netherlands, and 0.48 (95% CI 0.30-0.78) in Sweden. We were unable to unequivocally identify the optimal age group for screening, as mortality reduction differed among centres and age groups. Instead, the screening effect appears to depend on screening duration, and the number and frequency of screening rounds. PCa mortality reduction by screening is largely attributable to stage shift.

Effects of joint screening for prostate, lung, colorectal, and ovarian cancer - results from a controlled trial.

Although screening is widely used to reduce cancer burden, untargeted cancers are frequently missed after single cancer screening. Joint cancer screening is presumed as a more effective strategy to reduce overall cancer burden. Gender-specific screening effects on PLCO cancer incidence, PLCO cancer mortality, all-neoplasms mortality and all-cause mortality were evaluated, and meta-analyses based on gender-specific screening effects were conducted to achieve the pooled effects. The cut-off value of time-dependent receiver-operating-characteristic curve of 10-year combined PLCO cancer risk was used to reclassify participants into low- and high-risk subgroups. Further analyses were conducted to investigate screening effects stratified by risk groups and screening compliance. After a median follow-up of 10.48 years for incidence and 16.85 years for mortality, a total of 5,506 PLCO cancer cases, 1,845 PLCO cancer deaths, 3,970 all-neoplasms deaths, and 14,221 all-cause deaths were documented in the screening arm, while 6,261, 2,417, 5,091, and 18,516 outcome-specific events in the control arm. Joint cancer screening did not significantly reduce PLCO cancer incidence, but significantly reduced male-specific PLCO cancer mortality (hazard ratio and 95% confidence intervals [HR(95%CIs)]: 0.88(0.82, 0.95)) and pooled mortality [0.89(0.84, 0.95)]. More importantly, joint cancer screening significantly reduced both gender-specific all-neoplasm mortality [0.91(0.86, 0.96) for males, 0.91(0.85, 0.98) for females, and 0.91(0.87, 0.95) for meta-analyses] and all-cause mortality [0.90(0.88, 0.93) for male, 0.88(0.85, 0.92) for female, and 0.89(0.87, 0.91) for meta-analyses]. Further analyses showed decreased risks of all-neoplasm mortality was observed with good compliance [0.72(0.67, 0.77) for male and 0.72(0.65, 0.80) for female] and increased risks with poor compliance [1.61(1.40, 1.85) for male and 1.30(1.13, 1.40) for female]. Joint cancer screening could be recommended as a potentially strategy to reduce the overall cancer burden. More compliance, more benefits. However, organizing a joint cancer screening not only requires more ingenious design, but also needs more attentions to the potential harms. NCT00002540 (Prostate), NCT01696968 (Lung), NCT01696981 (Colorectal), NCT01696994 (Ovarian).

Development and validation of an imageless machine-learning algorithm for the initial screening of prostate cancer.

Prostate specific antigen (PSA) testing is a low-cost screening method for prostate cancer (PCa). However, its accuracy is limited. While progress is being made using medical imaging for PCa screening, PSA testing can still be improved as an easily accessible first step in the screening process. We aimed to develop and validate a new model by further personalizing the analysis of PSA with demographic, medical history, lifestyle parameters, and digital rectal examination (DRE) results. Using data from 34,224 patients in the screening arm of the PLCO trial (22,188 for the training set and 12,036 for the validation set), we applied a gradient-boosting model whose features (Model 1) were one PSA value and the personal variables available in the PLCO trial except those that signaled an ex-anteassumption of PCa. A second algorithm (Model 2) included a DRE result. The primary outcome was the occurrence of PCa, while the aggressiveness of PCa was a secondary outcome. ROC analyses were used to compare both models to other initial screening tests. The areas under the curve(AUC) for Model 2 was 0.894 overall and 0.908 for patients with a suspicious DRE, compared to 0.808 for PSA for patients with a suspicious DRE. The AUC for Model 1 was 0.814 compared to 0.821 for PSA. Model 2 predicted 58% more high-risk PCa than PSA ≥4 combined with an abnormal DRE and had a positive predictive value of 74.7% (vs. 50.6%). Personalizing the interpretation of PSA values and DRE results with a gradient-boosting model showed promising results as a potential novel, low-cost method for the initial screening of PCa. The importance of DRE, when included in such a model, was also highlighted.

Abstract 4798: MRI screening for brain metastases (BrM) versus SYMptom-directed brain imaging for patients with triple negative (TN) or HER2+ metastatic breast cancer (MBC): An ad-hoc interim analysis of a randomized phase II pilot study

Abstract Background: Patients with HER2+ or TN MBC are at high risk of developing BrM, but the role of MRI screening for early detection of asymptomatic BrM has not yet been established. Methods: We conducted a multicentre phase II pilot study, which randomized patients with TN or HER2+ MBC to 1 year of BrM screening (contrast enhanced brain MRI at baseline, 4, 8, and 12 months) versus a control arm of symptom directed brain imaging (MRI only if symptoms of BrM develop). The primary goal was to determine the feasibility of a future randomized trial of BrM screening versus symptom-directed imaging in this patient population. Key inclusion criteria were age ≥18; TN MBC diagnosed ≤12 weeks prior to study entry or HER2+ MBC with no restrictions regarding time of diagnosis; no symptoms of BrM or known asymptomatic BrM; ECOG ≥ 1 and no MRI contraindications. Overall (EORTC QLQ BN20) and neurologic-specific (FACT-BR tools) quality-of-life as well as cancer-related anxiety (NCI PRO-CTCAE) were assessed at baseline, 6 and 15 months. Criteria rendering a future trial “not feasible” were defined a-priori as: <30% of eligible patients enroll in the study, <50% complete the study protocol, and/or >50% of patients allocated to the control arm during the 1 year study period are screened for asymptomatic BrM with CT or MRI. Results: Between 2018 and 2023, 44 patients from 3 participating centres enrolled in the study. Thirty-five participants (80%) had HER2+ and 9 (20%) had TN MBC. Of the 22 patients randomized to each of the study arms; 3 patients (8%) in each arm withdrew prior to study completion. Reasons for withdrawal included claustrophobia (n=3) or discontent with their randomised arm (n=3) or follow-up requirements (n=1). Metrics regarding the proportion of eligible patients who enrolled in the study were only collected from the Sunnybrook Odette Cancer Centre site; of 91 patients approached, 38 (42%) enrolled in the study. Within the 12-month study period, the incidence of BrM among patients in the screening arm was n=3 (14%) versus n=4 (18%) in the control arm. To-date among patients in the study arm, 11 (50%) completed the 12-month screening protocol, 5 (23%) remain on study and 6 (27%) did not complete the protocol due to either death or early study withdrawal. Among patients in the control arm, 10 (45%) completed 12-month follow-up, 4 (18%) remain on study and 8 (36%) did not complete follow-up due to either death or early study withdrawal. In total, 13 patients (59%) in the control arm had brain imaging, 4 in the absence of neurological symptoms. Conclusion: A large randomized trial to investigate the utility of MRI-based surveillance for asymptomatic detection of BrM in the proposed patient population is likely feasible, although episodic brain imaging in the control arm was common. Analysis of patient reported outcomes is ongoing. Citation Format: Katarzyna Joanna Jerzak, Megan Shum, Gregory Pond, Orit Freedman, Gursimran Chandhoke, Tatiana Conrad, Priscilla Brastianos, Gregory Stanisz, Arjun Sahgal, Ellen Warner. MRI screening for brain metastases (BrM) versus SYMptom-directed brain imaging for patients with triple negative (TN) or HER2+ metastatic breast cancer (MBC): An ad-hoc interim analysis of a randomized phase II pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4798.

Utah gets license for masters in addiction counseling

It took two years of work and a 50‐page report, but Richard Nance got Utah to create a new Office of Professional License Review to be the screening arm of the Division of Professional Licensure. Any new license had to go through an application and review process, he told ADAW. “We were the first,” said Nance, former president of the Association of Utah Substance Abuse Professionals (AUSAP). “In 2023, I had my senator run the [Medication Aide Certified] MAC license bill, but the head of the Senate Business and Labor Committee refused to allow it a committee hearing because it ‘hadn't been through the OPLR process.’ There wasn't an OPLR process yet. Once it was created, I spent the summer of 2023 writing the application and working with the OPLR people to fix errors in the process,” Nance said.

Effect of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on incidence of these infections in men who have sex with men and transgender women taking HIV pre-exposure prophylaxis (the Gonoscreen study): results from a randomised, multicentre, controlled trial

Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP. A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed. Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported. We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population. Belgian Health Care Knowledge Centre.

The quality of life of frequently vs. infrequently screened HPV vaccinated women

PurposeCervical lesions caused by human papillomavirus (HPV) are related to decreased quality of life (QoL) of women. Also, cervical cancer (CC) screening can cause psychological adverse effects. It has been assumed that by decreasing the HPV-related disease burden, HPV vaccinations would increase the QoL. This study compares the effect of CC screening on QoL of HPV vaccinated women in two different screening protocols.MethodsA total of 753 HPV16/18 vaccinated women were randomized to frequent (22/25/28 years of age) and infrequent (28 years of age) CC screening arms. QoL questionnaires (EQ VAS, RAND 36, amended CECA 10) were sent at the age of 28.ResultsMedian EQ VAS scores were 80 (Q1–Q3 75–90) in both screening arms. Mean RAND 36 scores of frequently and infrequently screened women were 78.13/81.64 in Physical role functioning domain and, respectively, 77.93/80.18 in Pain, 69.10/69.12 in General Health, 54.67/53.61 in Energy, 83.72/85.11 in Social functioning, 69.53/69.68 in Emotional role functioning, and 68.16/69.29 in Emotional well-being domain. Among women with a self-reported history of Pap cytology abnormalities, overall mean scores of amended CECA 10 were 69.52/72.07, and among women with a self-reported history of genital warts, 60.09/66.73, respectively.ConclusionThere was no significant difference in the QoL of HPV vaccinated women between the two CC screening arms. Women were mostly satisfied with the screening experience despite the screening frequency. This information is important for the future screening program planning as we need to reach the best possible balance with screening benefits and harms.Trial registration numberNCT02149030, date of registration 29/5/2014.

Early detection of clinically significant prostate cancer: protocol summary and statistical analysis plan for the ProScreen randomised trial

IntroductionEvidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis, and complications from biopsies...

Similar effectiveness with primary HPV and cytology screening - Long-term follow-up of randomized cervical cancer screening trial

BackgroundLong-term effects of primary human papillomavirus (HPV) screening on cervical cancer incidence and mortality are still missing. We conducted a long-term follow-up of the Finnish randomized HPV screening trial, the first HPV screening trial run within the routine screening program, to assess these measures. MethodsDuring 2003–2008, over 236,000 individuals were randomized (1:1) to HPV and cytology screening arms in Southern Finland. To compare the study arms, we calculated the cervical cancer incidence and mortality rate ratios using Poisson regression. ResultsDuring a total of 3.5 million person-years of follow-up, we observed 129 cervical cancers and 32 cervical cancer deaths in the cytology arm, 139 cervical cancers and 32 cervical cancer deaths in the HPV arm. Compared to the cytology arm, in the HPV arm, the incidence rate ratio was 1.08 (95% CI 0.85–1.37), and the mortality rate ratio was 1.01 (95% CI 0.61–1.64). ConclusionsWe studied the effects of HPV screening on both cervical cancer incidence and mortality for the first time in a setting with an already well-established, high-quality cytology screening program. In this kind of setting with a low incidence of cervical cancer, HPV and cytology screening showed similar effectiveness. HPV screening provides, however, an objective, validated test system and enables self-sampling which can improve screening coverage. More attention is needed yet to ensure the balance between the harms and benefits of HPV screening.

Screening history and risk of death from prostate cancer: a nested case–control study within the screening arm of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC)

PurposeWe assessed the risk of death from prostate cancer (PCa) in relation to men’s screening histories, i.e., screening attendance among men who were offered screening.MethodsMen in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) screening arm were invited to up to three screening rounds with the serum prostate-specific antigen (PSA) test at 4-year intervals during 1996–2007.Case subjects (n = 330) were men who died from PCa. Each case was matched to five controls (n = 1544) among the men who were free of PCa.Screening history was defined as (1) never/ever attended screening prior to the case diagnosis; (2) attended at the first screening round; and (3) recency of screening, calculated as the time from last screening attendance to the date of case diagnosis.The association between screening history and the risk of death from PCa was estimated by odds ratios (OR) with 95% confidence intervals (CI) using conditional logistic regression.ResultsHaving ever attended screening versus never attended was associated with a reduced risk of PCa death (OR 0.60, 95% CI 0.45–0.81) and a similar association was found for those attended (versus not attended) the first screening round (OR 0.67, 95% CI 0.51–0.87).The effect by time since last screen for the risk of PCa death was significantly lower 2–7 years since last screen.ConclusionAmong men invited to screening, subjects who attended any PSA screening during the previous 19 years had a 40% reduction in PCa mortality compared to non-screened men.

Serum-based biomarkers associated with lung cancer risk and cause-specific mortality in the German randomized Lung Cancer Screening Intervention (LUSI) trial.

Lung cancer (LC) screening can be optimized using individuals' estimated risks of having a detectable lung tumor, as well as of mortality risk by competing causes, to guide decisions on screening eligibility, ideal screening intervals and stopping ages. Besides age, sex and smoking history, blood-based biomarkers may be used to improve the assessment of LC risk and risk of mortality by competing causes. In the German randomized Lung Screening Intervention Trial (LUSI), we measured growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), C-reactive protein (CRP) and N-terminal pro-brain natriuretic protein (NT-proBNP), in blood serum samples collected at start of the trial. Participants in the computed tomography (CT)-screening arm also had a pulmonary function test. Regression models were used to examine these markers as predictors for impaired lung function, LC risk and mortality due to LC or other causes, independently of age, sex and smoking history. Our models showed increases in LC risk among participants with elevated serum levels of GDF-15 [odds ratio (OR)Q4-Q1 =2.47, 95% confidence interval (CI): 1.49-4.26], IL-6 [ORQ4-Q1 =2.36 (1.43-4.00)] and CRP [ORQ4-Q1 =1.81 (1.08-2.75)]. Likewise, proportional hazards models showed increased risks for LC-related mortality, hazard ratio (HR)Q4-Q1 of 4.63 (95% CI: 2.13-10.07) for GDF-15, 3.56 (1.72-7.37) for IL-6 and 2.34 (1.24-4.39) for CRP. All four markers were associated with increased risk of mortality by causes other than LC, with strongest associations for GDF-15 [HRQ4-Q1 =3.04 (2.09-4.43)] and IL-6 [HRQ4-Q1 =2.98 (2.08-4.28)]. Significant associations were also observed between IL-6, CRP, GDF-15 and impaired pulmonary function [chronic obstructive pulmonary disease (COPD), preserved ratio impaired spirometry (PRISm)]. Multi-marker models identified GDF-15 and IL-6 as joint risk predictors for risk of LC diagnosis, without further discrimination by CRP or NT-proBNP. A model based on age, sex, smoking-related variables, GFD-15 and IL-6 provided moderately strong discrimination for prediction of LC diagnoses within 9 years after blood sampling [area under the curve (AUC) =74.3% (57.3-90.2%)], compared to 67.0% (49.3-84.8%) for a model without biomarkers. For mortality by competing causes, a model including biomarkers resulted in an AUC of 76.2% (66.6-85.3%)], compared to 70.0% (60.9-77.9%) a model including age, sex and smoking variables. Serum GDF-15 and IL-6 may be useful indicators for estimating risks for LC and competing mortality among long-term smokers participating in LC screening, to optimize LC screening strategies.