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Reproducibility of measurements of potential doubling time of tumour cells in the multicentre National Cancer Institute protocol T92-0045
Authors
AC Begg
AC Begg
+32 more
AC Begg
AC Begg
B Dubray
G D Wilson
GD Wilson
GG Steel
HR Withers
J Bourhis
J-J Pavy
JC Horiot
JF Fowler
JF Fowler
K Haustermans
K Weber
LJ Peters
LL Wheeless
LL Wheeless
MH Bennett
MJ Bland
MS Wilson
MS Wilson
N Paschoud
NHA Terry
P A Coucke
P Weber
R Corvo
RA White
RA White
RW Tsang
S Dische
SE Shackney
TV Shankey
Publication date
1 January 1999
Publisher
Nature Publishing Group
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PubMed
Abstract
We compared the flow cytometric measurement and analysis of the potential doubling time (Tpot) between three centres involved in the National Cancer Institute (NCI) protocol T92-0045. The primary purpose was to understand and minimize the variation within the measurement. A total of 102 specimens were selected at random from patients entered into the trial. Samples were prepared, stained, run and analysed in each centre and a single set of data analysed by all three centres. Analysis of the disc data set revealed that the measurement of labelling index (LI) was robust and reproducible. The estimation of duration of S-phase (Ts) was subject to errors of profile interpretation, particularly DNA ploidy status, and analysis. The LI dominated the variation in Tpot such that the level of final agreement, after removal of outliers and ploidy agreement, reached correlation coefficients of 0.9. The sample data showed poor agreement within each of the components of the measurement. There was some improvement when ploidy was in agreement, but correlation coefficients failed to exceed values of 0.5 for Tpot. The data suggest that observer-associated analysis of Ts and tissue processing and tumour heterogeneity were the major causes of variability in the Tpot measurement. The first two aspects can be standardized and minimized, but heterogeneity will remain a problem with biopsy techniques. © 1999 Cancer Research Campaig
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