PMID- 18794099
OWN - NLM
STAT- MEDLINE
DCOM- 20081008
LR  - 20191210
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 18
DP  - 2008 Sep 15
TI  - Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal 
      cancer patients treated with cetuximab: a fluorescent in situ hybridization 
      study.
PG  - 5869-76
LID - 10.1158/1078-0432.CCR-08-0449 [doi]
AB  - PURPOSE: To evaluate the usefulness and the pitfalls inherent to the assessment 
      of the epidermal growth factor receptor (EGFR) gene copy number (GCN) by 
      fluorescence in situ hybridization (FISH) for outcome prediction to cetuximab in 
      metastatic colorectal cancer. The value of testing KRAS mutation status, in 
      addition to EGFR GCN, was also explored. EXPERIMENTAL DESIGN: FISH analysis of 87 
      metastatic colorectal cancer patients treated with cetuximab was done, recording 
      individual GCN per cell and using different samples per tumor. Performances of 
      published cutoff points and different summaries of EGFR GCN distribution were 
      assessed for response prediction. RESULTS: In our data set, two published cutoff 
      points performed less well than in their training set, yielding positive 
      predictive values and negative predictive values between 40.0% and 48.3% and 
      between 81.0% and 86.5%, respectively. Among summaries of GCN distribution 
      explored, mean and right-tailed distribution of GCN yielded the highest 
      performances. A mean EGFR GCN > or = 2.83 provided an area under the curve of 
      0.71. Important heterogeneity of repeated measures of mean EGFR GCN was observed 
      within tumors (intraclass correlation, 0.61; within-class SD, 0.40), leading to 
      potential misclassifications of FISH status in 7 of 18 (38.8%) patients if a 
      cutoff point were used. In multivariable analysis, EGFR GCN testing provided 
      significant information independent of the KRAS status to predict response (P = 
      0.016) and overall survival (P = 0.005). CONCLUSIONS: We confirm the association 
      between increased EGFR GCN and outcome after cetuximab. However, because of 
      reproducibility concerns, any decision making based on published cutoff points is 
      not warranted.
FAU - Personeni, Nicola
AU  - Personeni N
AD  - Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium.
FAU - Fieuws, Steffen
AU  - Fieuws S
FAU - Piessevaux, Hubert
AU  - Piessevaux H
FAU - De Hertogh, Gert
AU  - De Hertogh G
FAU - De Schutter, Jef
AU  - De Schutter J
FAU - Biesmans, Bart
AU  - Biesmans B
FAU - De Roock, Wendy
AU  - De Roock W
FAU - Capoen, An
AU  - Capoen A
FAU - Debiec-Rychter, Maria
AU  - Debiec-Rychter M
FAU - Van Laethem, Jean-Luc
AU  - Van Laethem JL
FAU - Peeters, Marc
AU  - Peeters M
FAU - Humblet, Yves
AU  - Humblet Y
FAU - Van Cutsem, Eric
AU  - Van Cutsem E
FAU - Tejpar, Sabine
AU  - Tejpar S
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Genetic Markers)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Cetuximab
MH  - Colorectal Neoplasms/*drug therapy/*genetics
MH  - Disease-Free Survival
MH  - Female
MH  - *Gene Dosage
MH  - *Genes, erbB-1
MH  - *Genetic Markers
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Prognosis
EDAT- 2008/09/17 09:00
MHDA- 2008/10/09 09:00
CRDT- 2008/09/17 09:00
PHST- 2008/09/17 09:00 [pubmed]
PHST- 2008/10/09 09:00 [medline]
PHST- 2008/09/17 09:00 [entrez]
AID - 14/18/5869 [pii]
AID - 10.1158/1078-0432.CCR-08-0449 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Sep 15;14(18):5869-76. doi: 10.1158/1078-0432.CCR-08-0449.