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Ras Mutational Status Predicts Patterns Of Recurrence And Survival In Patients Undergoing Hepatectomy For Colorectal Liver Metastases
Jean-Nicolas Vauthey, Giuseppe Zimmitti*, Junichi Shindoh*, Su S. Chen*, Scott Kopetz*, Andreas Andreou*, Steven S. Curley, Thomas A. Aloia*, Dipen M. Maru*
MD Anderson Cancer Center, Houston, TX

OBJECTIVE(S):
RAS mutations in colorectal cancer are associated with worse tumor biology. However, their effect on outcomes after resection of colorectal liver metastases (CLM) remains unclear.
METHODS:
CLM from 193 patients treated with single-regimen modern chemotherapy before hepatic resection were assessed for somatic mutations using mass spectroscopy. Relationships between RAS mutation status, recurrence patterns and survivals were investigated.

RESULTS:
Identified mutations included RAS (KRAS/NRAS) in 34 patients (18%), PIK3CA in 13 (7%), and BRAF in 2 (1%). At a median follow-up of 33 months, 3-year recurrence-free survivals (RFS) were 33.5% in RAS wild-type vs. 13.5% in RAS mutant patients (p=0.001). RAS mutant patients experienced shorter 3-year lung RFS (34.6% vs. 59.3%, p<0.001), while liver RFS was not influenced by RAS status (43.8% vs. 50.2%, p=0.181) (Figure). 3-year overall survivals (OS) were 81% in RAS wild-type vs. 52.2% in RAS mutant patients (p=0.002). Multivariate analyses determined that RAS mutation was independently associated with worse OS (HR 2.3, p=0.02), overall RFS (HR 1.9, p=0.005), and lung RFS (HR 2.0, p=0.01), but not liver RFS (p=0.348).

CONCLUSIONS:
The novel finding of this study is that RAS mutation not only predicts worse survivals, but also a lung-specific recurrence pattern after curative resection of CLM.


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