Publications by authors named "N Aaronson"

491 Publications

A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Lancet Oncol 2021 11 19;22(11):1618-1631. Epub 2021 Oct 19.

University Hospital Southampton, Southampton, UK; Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.

Background: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants.

Methods: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This study is registered with ClinicalTrials.gov, NCT00261456, and is now closed to accrual.

Findings: Between Sept 28, 2012, and March 1, 2020, 828 men were recruited (644 carriers of mismatch repair pathogenic variants [204 carriers of MLH1, 305 carriers of MSH2, and 135 carriers of MSH6] and 184 non-carrier controls [65 non-carriers of MLH1, 76 non-carriers of MSH2, and 43 non-carriers of MSH6]), and in order to boost the sample size for the non-carrier control groups, we randomly selected 134 non-carriers from the BRCA1 and BRCA2 cohort of the IMPACT study, who were included in all three non-carrier cohorts. Men were predominantly of European ancestry (899 [93%] of 953 with available data), with a mean age of 52·8 years (SD 8·3). Within the first screening round, 56 (6%) men had a PSA concentration of more than 3·0 ng/mL and 35 (4%) biopsies were done. The overall incidence of prostate cancer was 1·9% (18 of 962; 95% CI 1·1-2·9). The incidence among MSH2 carriers was 4·3% (13 of 305; 95% CI 2·3-7·2), MSH2 non-carrier controls was 0·5% (one of 210; 0·0-2·6), MSH6 carriers was 3·0% (four of 135; 0·8-7·4), and none were detected among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls. Prostate cancer incidence, using a PSA threshold of higher than 3·0 ng/mL, was higher in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%; p=0·011) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%; p=0·034). The overall positive predictive value of biopsy using a PSA threshold of 3·0 ng/mL was 51·4% (95% CI 34·0-68·6), and the overall positive predictive value of a PSA threshold of 3·0 ng/mL was 32·1% (20·3-46·0).

Interpretation: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings.

Funding: Cancer Research UK, The Ronald and Rita McAulay Foundation, the National Institute for Health Research support to Biomedical Research Centres (The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Oxford; Manchester and the Cambridge Clinical Research Centre), Mr and Mrs Jack Baker, the Cancer Council of Tasmania, Cancer Australia, Prostate Cancer Foundation of Australia, Cancer Council of Victoria, Cancer Council of South Australia, the Victorian Cancer Agency, Cancer Australia, Prostate Cancer Foundation of Australia, Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), the Institut Català de la Salut, Autonomous Government of Catalonia, Fundação para a Ciência e a Tecnologia, National Institutes of Health National Cancer Institute, Swedish Cancer Society, General Hospital in Malmö Foundation for Combating Cancer.
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http://dx.doi.org/10.1016/S1470-2045(21)00522-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576477PMC
November 2021

Characteristics of Participants and Nonparticipants in a Blended Internet-Based Physical Activity Trial for Breast and Prostate Cancer Survivors: Cross-sectional Study.

JMIR Cancer 2021 Oct 5;7(4):e25464. Epub 2021 Oct 5.

Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, Netherlands.

Background: As the number of cancer survivors is increasing, it is important to be able to offer exercise and physical activity (PA)-promoting interventions that are both effective and reasonably accessible. Internet-based interventions are typically less expensive and more accessible alternatives to on-site supervised interventions. Currently, little is known about the characteristics of nonparticipants in PA promotion trials in the cancer survivorship setting, both in general and specifically in trials using internet-supported interventions.

Objective: This study aims to gain insight into the characteristics associated with nonparticipation in a blended internet-based supported intervention trial to promote PA.

Methods: Breast and prostate cancer survivors, 3-36 months after primary curative treatment, were invited to participate in the PABLO trial; this trial compared an internet-based intervention to enhance PA levels, with or without additional support from a physical therapist, to usual care. Participants and nonparticipants were asked to complete a comprehensive questionnaire assessing sociodemographics, fatigue, and health-related quality of life. Baseline data for participants and nonparticipants were compared using the independent Student t test and chi-square test.

Results: The inclusion rate in the trial was 11.03% (137/1242). Of the nonparticipants, 13.95% (154/1104) completed the questionnaire. Participants were more highly educated (P=.04), had a paid job less often (P=.03), and were on sick leave more often (P=.03). They reported less PA per week, both moderate (P=.03) and vigorous (P<.01), before diagnosis and during leisure time (P<.01, effect size [ES]=0.44). They reported a significantly lower stage of change (P≤.01), lower self-efficacy (P<.01, ES=0.61), perceived barriers to PA (P<.01, ES=0.54), and more general fatigue (P<.01, ES=0.60). Participants reported lower health-related quality of life for most domains (ES ranging from 0.34 for mental health to 0.48 for social functioning). No significant differences were found for other sociodemographics, mood state, or attitudes toward or perceived social support for PA.

Conclusions: The participants who self-selected for trial participation reported lower PA levels before diagnosis and a stronger need for support compared with nonparticipants. The trial thus included those patients who might benefit the most from internet-based supportive PA interventions.

Trial Registration: Netherlands trial register NTR6911; https://www.trialregister.nl/trial/6733.
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http://dx.doi.org/10.2196/25464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527379PMC
October 2021

Validation and reliability of the Dutch version of the EORTC QLQ-NMIBC24 Questionnaire Module for patients with non-muscle-invasive bladder cancer.

J Patient Rep Outcomes 2021 Sep 20;5(1):96. Epub 2021 Sep 20.

Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire for non-muscle invasive bladder cancer (QLQ-NMIBC24) has been available and applied for some years now, but has yet to undergo a full comprehensive psychometric evaluation. The aim of this study was to investigate the psychometric properties of the Dutch version of the EORTC QLQ-NMIBC24 questionnaire in patients with low, intermediate and high risk NMIBC.

Methods: We included patients newly diagnosed with NMIBC participating in the multicenter, population-based prospective cohort studies UroLife or BlaZIB. Psychometric evaluation included examination of the structural validity, reliability (i.e. internal consistency and test-retest reliability), construct validity (i.e. divergent validity and known-groups validity), responsiveness and interpretability.

Results: A total of 1463 patients who completed the baseline questionnaire of UroLife (n = 541, response rate 50%) or BlaZIB (n = 922, response rate 58%) were included. The percentage of missing responses were low for all non-sex related scales (< 1%) and ranged between 6.9% to 50.0% for sex-related scales. More than 15% of the patients obtained the lowest possible scores on nearly each scale (floor effect). The structural validity was adequate; the confirmatory factor analysis showed satisfactory results and all items of multiple items scales had higher within- than between-scale correlations. Reliability of the questionnaire was adequate for most multiple item scales (Cronbach's α ≥ 0.70 and intraclass correlation coefficient ≥ 0.70), with exception of the scales 'malaise' and 'bloating and flatulence'. The questionnaire also showed good construct validity; it showed low correlations with the items of the EORTC core questionnaire and was able to measure differences between risk-based subgroups. The responsiveness of the questionnaire was good, but the interpretability, i.e. minimal important change, could not be determined.

Conclusions: This study shows that the measurement properties of the EORTC QLQL-NMIBC24 are good; it has a good structural validity, reliability (i.e. internal consistency and test-retest reliability), construct validity (i.e. divergent validity and known-group validity), and responsiveness. Interpretability could not be assessed. This questionnaire can be used to measure and monitor health-related quality of life of patients with NMIBC.
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http://dx.doi.org/10.1186/s41687-021-00372-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452806PMC
September 2021

SYMptom monitoring with Patient-Reported Outcomes using a web application among patients with Lung cancer in the Netherlands (SYMPRO-Lung): study protocol for a stepped-wedge randomised controlled trial.

BMJ Open 2021 09 13;11(9):e052494. Epub 2021 Sep 13.

Department for Health Evidence, Radboud University Medical Center, Nijmegen, Gelderland, The Netherlands.

Introduction: Lung cancer and its treatment cause a wide range of symptoms impacting the patients' health-related quality of life (HRQoL). The use of patient-reported outcomes (PRO) to monitor symptoms during and after cancer treatment has been shown not only to improve symptom management but also to improve HRQoL and overall survival (OS). Collectively, these results favour implementation of PRO-symptom monitoring in daily clinical care. However, these promising outcomes have been obtained under trial conditions in which patients were selected based on stringent inclusion criteria, and in countries with a dissimilar healthcare system than in the Netherlands.The primary aim of the SYMptom monitoring with Patient-Reported Outcomes using a web application among patients with Lung cancer in the Netherlands (SYMPRO-Lung) study is to evaluate the effect of PRO-symptom monitoring during and after lung cancer treatment on HRQoL in daily clinical practice. Secondary objectives include assessing the effect of PRO-symptom monitoring on progression-free survival, OS, the incidence and grade of PRO symptoms, medication adherence, implementation fidelity and cost-effectiveness.

Methods And Analysis: The SYMPRO-Lung study is a prospective, multicentre trial with a stepped wedge cluster randomised design. Study participants (n=292 intervention, n=292 controls) include patients with lung cancer (stages I-IV) starting treatment with surgery, systemic treatment, targeted treatment and/or radiotherapy.Every participating centre will consecutively switch from the control period to the intervention period, in which patients report their symptoms weekly via an online tool. In the intervention group, we evaluate two alert approaches: the active and reactive approach. If the symptoms exceed a predefined threshold, an alert is sent to the healthcare provider (active approach) or to the patient (reactive approach). Both the control and intervention group complete HRQoL questionnaires at 4 time points: at baseline, 15 weeks, 6 months and 1-year post treatment). Differences in HRQoL between the groups will be compared using linear mixed modelling analyses, accounting for within-centre clustering, potential time effects and confounding.

Ethics And Dissemination: The study protocol was approved by the Institutional Review Board and the Medical Ethics Committee of the Amsterdam UMC (under number NL 68440.029.18) and the institutional review boards of the participating study sites. The dissemination of the results will be conducted through publication in peer-reviewed journals and through scientific conferences.

Trial Registration Number: Trial register identifier: Netherlands Trial register Trial NL7897. Date of registration: 24 July 2019. https://www.trialregister.nl/trial/7897.
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http://dx.doi.org/10.1136/bmjopen-2021-052494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438957PMC
September 2021

Impact of Blinding on Patient-Reported Outcome Differences between Treatment Arms in Cancer Randomized Controlled Trials.

J Natl Cancer Inst 2021 Sep 11. Epub 2021 Sep 11.

University Hospital of Psychiatry II, Medical University of Innsbruck, Innsbruck, Austria.

Some concerns have been raised about potential bias in patient-reported outcome (PRO) results from open-label cancer randomized controlled trials (RCTs). We investigated if open-label trials favor the experimental treatment over the standard treatment more frequently than blinded trials. We also examined if the effect of treatment concealment differs for distal vs more proximal PROs. We assessed 538 RCTs with a PRO endpoint conducted in the most prevalent cancers, of which 366 (68.0%) were open-label, 148 (27.5%) were blinded, and 24 (4.5%) were categorized as unclear. In our multivariable logistic regression model, we did not observe a statistically significant association of the independent variable treatment concealment (open-label vs blinded) on the dependent variable measuring the proportion of trials favoring the experimental treatment (adjusted odds ratio = 1.19, 95% confidence interval = 0.79 to 1.79, 2-sided P = .40. This was also the case when comparing distal and proximal PROs. Our findings provide novel evidence-based data that support the validity of PRO results from open label cancer RCTs.
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http://dx.doi.org/10.1093/jnci/djab177DOI Listing
September 2021
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