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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

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.
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.

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).

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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