Biomedical Engineering Reference
In-Depth Information
as ≤16 repeats) and superior response and survival than patients
with >16
84
Similar results were demonstrated in a study
of 92 gefitinib treated patients, with patients carrying shorter
CA
repeats.
CA
85
repeats enjoying a superior PFS than patients with longer repeats.
Huang
et al.
described an association with shorter
CA
repeat and
86
the presence of skin rash.
However, this was not the finding when
evaluated using 242 samples collected as part of the NCIC CTG BR.21
clinical trial in which patients with at least one short allele (<16
repeats) randomized to the placebo had an improved PFS compared
with those patients that had homozygous long alleles, whereas no
association for patients randomized to the erlotinib arm.
87
This may
indicate that
intron 1 CA
repeats has prognostic but not predictive
significance.
Other
EGFR
polymorphisms of interest include
-216G/T
and
-191C/A
, which are located in the gene promoter at transcription
factor binding sites including SP1.
88
Again, studies that have
evaluated the association between these genetic polymorphisms
and outcome have reported inconsistent results
; however, these
were not shown to be predictive of benefit from erlotinib when
evaluated retrospectively as part of the BR.21 clinical trial.
89,90
87
While germline polymorphisms may contribute to the
understanding of variation in benefit and toxicity experienced
by patients on EGFR TKIs, results are inconsistent and currently
exploratory in nature. Studies conducted in small cohorts of patients
may have contributed to the inconsistent findings and further studies
are needed to define the role of germline variation and outcome and
toxicity of EGFR inhibitory agents.
6.11
Circulating Tumor Cells in NSCLC
Biomarker Research
Successful evaluation of tumor biomarkers requires adequate tissue
sampling in order to perform the required analysis. Unfortunately,
tissue acquisition has been limited in NSCLC. Frequently, the initial
diagnosis of advanced disease is generally made utilizing fine-needle
aspiration or bronchial washing methods; unfortunately, these
techniques make it more difficult to acquire an adequate sample
for molecular analysis. For example, fewer than 50% of patients
in the BR21, INTEREST and IPASS clinical trials were evaluated for
