Statistical effects of varying sample sizes on the precision of percentile estimates

The present study evaluates the precision of outlying percentile estimates, with age- and sex-associated variations and facilitates decisions needed to revise the current NCHS 1977 Growth Charts with regard to 1) the inclusion of 3^rd and 97^th percentiles and 2) the selection of survey data for the construction of the revised growth charts. Simulation was performed to obtain data with distribution characteristics similar to those of The Third National Health and Nutritional Examination Survey (NHANES III) (1988–1991) data. NHANES III consists of a two-phase, 6-year, complex stratified multistage probability cluster, cross-sectional survey conducted from 1988 through 1994 to represent the US noninstitutionalized population. Phase I of the survey consisted of 679 boys and 622 girls in age groups 3, 8, 13, and 18 years. Weight and stature, the body mass index (BMI) (weight/stature²; kg/m²) was calculated. The results show that 1) the precision of the percentile estimates is greater for stature than for weight and BMI, 2) percentiles during the pubertal period are less precise than those during the prepubertal and postpubertal periods for weight and BMI but there is little difference for stature, and 3) percentile estimates are more precise for girls than boys for weight and BMI, but not for stature. The present findings suggest that pooling of NHANES III and earlier National Center for Health Statistics (NCHS) survey data is necessary to achieve reasonable precision for the 3^rd and 97^th percentile estimates. Am. J. Hum. Biol. 12:64–74, 2000. © 2000 Wiley-Liss, Inc.     

Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer

Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24–71) (8/17), specificity of 85% (95% CI 42–99) (6/7), positive predictive value (PPV) of 89% (95% CI 51–99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17–67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6–51) (3/14), specificity of 100% (95% CI 56–100) (7/7), PPV of 100% (95% CI 31–100) (3/3), and NPV of 39% (95% CI 18–64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.