Biomedical Engineering Reference
In-Depth Information
metastatic lesions from the same patient, suggesting that evaluation
of
status can be performed in either the primary tumor or
metastatic sites [68]. Similarly, a recent study demonstrated a
concordance of 90% between primary and distant metastases for
KRAS
KRAS
mutations detected by direct sequencing and pyro-sequencing
techniques [69]. Based on the high concordance rate, guidelines have
been formulated suggesting that primary lesions, if metastatic tissue
is not available, be tested for
mutations prior to utilizing an
anti-EGFR moAb. However, it remains unclear whether there should
be attempts to determine the
KRAS
status in the untested primary or
metastatic tissue, if the tested sample is
KRAS
KRAS
WT. Also, whether the
KRAS
discordance affects its predictive role remains unknown.
7.4.2.4 Prognostic significance of KRAS mutation status
There have been discrepant reports on the prognostic significance
of
mutations with some suggestion that KRAS mutations
may be prognostic in the earlier stages of colorectal cancer but not
in the metastatic setting. Earlier studies have demonstrated that
KRAS
KRAS
mutations portend a poorer prognosis in patients with non-
metastatic stages of colorectal cancer [70-72]. Some of these earlier
smaller studies may have been subject to publication bias, as more
recent analyses from the CALGB 89803 [73] and the PETACC-3
[74] trials demonstrate that KRAS mutations are not prognostic for
patients with stage 2 or 3 colorectal cancer treated with adjuvant
5-fluoruracil based chemotherapy. Finally, a trial investigating the
role of cetuximab in chemotherapy pre-treated patients with mCRC
did not demonstrate a prognostic effect for KRAS status in those
patients randomized to receive best supportive care [75]. Although
debatable, there is evidence to suggest that there may be a prognostic
role for patients with earlier stages of colorectal cancer and none for
those with mCRC.
7.4.2.5
Predictive significance of KRAS mutation status
Despite
mutations having questionable prognostic value in
patients with mCRC, it is certainly predictive of treatment benefit
in this setting. The presence of
KRAS
mutations correlates with lack
of objective response rate and improvement in both progression
free and overall survival in patients with mCRC who received anti-
EGFR moAbs. Interestingly, in a study of 30 patients with mCRC,
all of the
KRAS
KRAS
mutations were harbored by patients who did not
