abstract
OBJECTIVES:
Cytoreductive
surgery is the cornerstone of ovarian cancer (OVCA) treatment.
Detractors of initial maximal surgical effort argue that aggressive
tumor biology will dictate survival, not the surgical effort. We
investigated the role of biology in achieving optimal cytoreduction in
serous OVCA using microarray gene expression analysis.
METHODS:
For
the initial model, we used a gene expression signature from a
microarray expression analysis of 124 women with serous OVCA, defining
optimal cytoreduction as removal of all disease greater than 1 cm (with
64 women having optimal and 60 suboptimal cytoreduction). We then
applied this model to 2 independent data sets: the Australian Ovarian
Cancer Study (AOCS; 190 samples) and The Cancer Genome Atlas (TCGA; 468
samples). We performed a second analysis, defining optimal cytoreduction
as removal of all disease to microscopic residual, using data from AOCS
to create the gene signature and validating results in TCGA data set.
RESULTS:
Of
the 12,718 genes included in the initial analysis, 58 predicted
accuracy of cytoreductive surgery 69% of the time (P = 0.005). The
performance of this classifier, measured by the area under the receiver
operating characteristic curve, was 73%. When applied to TCGA and AOCS,
accuracy was 56% (P = 0.16) and 62% (P = 0.01), respectively, with
performance at 57% and 65%, respectively. In the second analysis, 220
genes predicted accuracy of cytoreductive surgery in the AOCS set 74% of
the time, with performance of 73%. When these results were validated in
TCGA set, accuracy was 57% (P = 0.31) and performance was at 62%.
CONCLUSION:
Gene
expression data, used as a proxy of tumor biology, do not predict
accurately nor consistently the ability to perform optimal cytoreductive
surgery. Other factors, including surgical effort, may also explain
part of the model. Additional studies integrating more biological and
clinical data may improve the prediction model.
0 comments :
Post a Comment
Your comments?
Note: Only a member of this blog may post a comment.