Considerable interlaboratory variation in PD-L1 positivity in a nationwide cohort of non-small cell lung cancer patients

Objectives: Immunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. Materials and Methods: Data on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands. PD-L1 positivity rates were determined for each laboratory that performed PD-L1 testing, with separate analyses for histological and cytological material. Two cutoffs (1% and 50%) were used to determine PD-L1 positivity. Differences between laboratories were assessed using funnel plots with 95% confidence limits around the overall mean. Results: 6,354 patients from 30 laboratories were included in the analysis of histology data. At the 1% cutoff, maximum interlaboratory variation was 39.1% (32.7%-71.8%) and ten laboratories (33.3%) differed significantly from the mean. Using the 50% cutoff, four laboratories (13.3%) differed significantly from the mean and maximum variation was 23.1% (17.2%-40.3%). In the analysis of cytology data, 1,868 patients from 23 laboratories were included. Eight laboratories (34.8%) differed significantly from the mean in the analyses of both cutoffs. Maximum variation was 41.2% (32.2%-73.4%) and 29.2% (14.7%-43.9%) using the 1% and 50% cutoffs, respectively. Conclusion: Considerable interlaboratory variation in PD-L1 positivity was observed. Variation was largest using the 1% cutoff. At the 50% cutoff, analysis of cytology data demonstrated a higher degree of variation than the analysis of histology data

Investigating International Time Trends in the Incidence and Prevalence of Atopic Eczema 1990-2010: A Systematic Review of Epidemiological Studies

The prevalence of atopic eczema has been found to have increased greatly in some parts of the world. Building on a systematic review of global disease trends in asthma, our objective was to study trends in incidence and prevalence of atopic eczema. Disease trends are important for health service planning and for generating hypotheses regarding the aetiology of chronic disorders. We conducted a systematic search for high quality reports of cohort, repeated cross-sectional and routine healthcare database-based studies in seven electronic databases. Studies were required to report on at least two measures of the incidence and/or prevalence of atopic eczema between 1990 and 2010 and needed to use comparable methods at all assessment points. We retrieved 2,464 citations, from which we included 69 reports. Assessing global trends was complicated by the use of a range of outcome measures across studies and possible changes in diagnostic criteria over time. Notwithstanding these difficulties, there was evidence suggesting that the prevalence of atopic eczema was increasing in Africa, eastern Asia, western Europe and parts of northern Europe (i.e. the UK). No clear trends were identified in other regions. There was inadequate study coverage worldwide, particularly for repeated measures of atopic eczema incidence. Further epidemiological work is needed to investigate trends in what is now one of the most common long-term disorders globally. A range of relevant measures of incidence and prevalence, careful use of definitions and description of diagnostic criteria, improved study design, more comprehensive reporting and appropriate interpretation of these data are all essential to ensure that this important field of epidemiological enquiry progresses in a scientifically robust manner

Alcohol and dietary folate intake and promoter CpG island methylation in clear-cell renal cell cancer

We investigated whether alcohol and dietary folate intakes were associated with promoter methylation in clear-cell renal cell carcinoma (ccRCC). The Netherlands Cohort Study with a case-cohort design included 120,852 subjects aged 55-69yr in 1986. Diet was measured with a food-frequency questionnaire. After 20.3yr of follow-up, paraffin-embedded tumor blocks were collected. Methylation-specific polymerase chain reaction (MSP) was used to analyze promoter methylation of 11 genes. ccRCC cases were classified into low (0-19% of the genes), intermediate (20-39%), and high (40%+) methylation. Multivariable Cox regression analyses were conducted, stratified according to methylation, including 3980 subcohort members and 297 ccRCC cases. Increasing alcohol intake was associated with decreased ccRCC risk, but was not statistically significant; multivariable adjusted hazard ratio (HR) for 30g alcohol/day versus 0 g/day was 0.78 [95% confidence interval (CI): 0.48-1.24], and P-value for trend was 0.46. In strata according to methylation index, no significant heterogeneity was observed. Dietary folate intake was not associated with ccRCC risk. There was no significant heterogeneity between strata according to methylation index. There was no effect modification of alcohol and dietary folate intake on ccRCC risk, nor in strata according to methylation index. Our findings do not support the hypothesis that alcohol and dietary folate intakes are involved in ccRCC

Primary and secondary outcomes measures.

<p>Primary and secondary outcomes measures.</p

Good and moderate quality studies reporting the incidence and prevalence of parental- or self-report of atopic eczema between 1990 and 2010 in Europe.

<p>Abbreviations – CI: confidence intervals, SE: standard error, POR: prevalence odds ratio, OR: odds ratio.</p>*<p>Based on UN classification <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039803#pone.0039803-United1" target="_blank">[16]</a>.</p>**<p>95% CI and SE are only reported if included in original report.</p>#<p>Point estimate extracted from graph or chart.</p

Good and moderate quality studies reporting the prevalence of parental- or self-report of atopic eczema between 1990 and 2010 in the Americas.

<p>Abbreviations – CI: confidence intervals, SE: standard error, OR: odds ratio.</p>*<p>Based on UN classification <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039803#pone.0039803-United1" target="_blank">[16]</a>.</p>**<p>95% CI and SE are only reported if included in original report.</p

Good and moderate quality studies reporting the prevalence of parental- or self-report of atopic eczema between 1990 and 2010 in Asia.

<p>Abbreviations – CI: confidence intervals, SE: standard error, OR: odds ratio, POR: prevalence odds ratio, PR: prevalence ratio.</p>*<p>Based on UN classification <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039803#pone.0039803-United1" target="_blank">[16]</a>.</p>**<p>95% CI or SE are only reported if included in original report.</p>#<p>Point estimate extracted from graph or chart.</p

Good and moderate quality studies reporting the prevalence of parental- or self-report of atopic eczema between 1990 and 2010 in Oceania.

<p>Abbreviations – CI: confidence intervals, SE: standard error, OR: odds ratio.</p>*<p>Based on UN classification <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039803#pone.0039803-United1" target="_blank">[16]</a>.</p>**<p>95% CI and SE are only reported if included in original report.</p>#<p>Point estimate extracted from graph or chart.</p