RAS mutation linked with survival in metastatic colorectal cancer

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1. Patients with colorectal liver metastases (CLM) with a RAS gene mutation were more likely to have cancer recurrence and had lower 3-year survival. 

2. Cancer recurrence in the lung was associated with RAS status, while liver recurrence was not. 

Evidence Rating Level: 2 (Good)            

Study Rundown: In this retrospective cohort study, authors used curative resection specimens from patients with hepatic colorectal metastases to demonstrate an association between RAS mutation and survival as well as cancer recurrence. Strengths of this study include robust sample size and narrow study criteria that only included patients with one round of preoperative chemotherapy with specific agents, thus ensuring participant homogeneity. Though 1406 consecutive CLM patients were treated at MD Anderson, only data from 193 patients was analyzed. The results are thus more difficult to generalize to many CLM patients who receive multiple rounds of preoperative chemotherapy or concomitant radiofrequency ablation.

Click to read the study in Annals of Surgery

Relevant Reading: KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer

In-Depth [retrospective cohort]: This study analyzed the RAS mutation status of 193 patients with curatively resected hepatic colorectal metastases between 1997 and 2011 with a median follow-up time of 33 months. All patients underwent one round of preoperative chemotherapy. Following laparotomy the resected specimens were examined for somatic mutations using Sequenom’s MassARRAY system. Forty-three patients (22.3%) had a mutation in one the genes assayed and 34 patients (17.6%) were positive for a RAS mutation. Patients with a RAS mutation has lower recurrence-free survival (RFS) at three years compared to patients with wild-type RAS (13.5% vs. 33.5%, p=0.001) and worse overall survival at three years (52.2% vs. 81%, p=0.002). RAS mutation along with poor pathologic response to neoadjuvant chemotherapy were identified as independent risk factors for RFS and overall survival. Tumor recurrence in the lung was also associated with RAS mutation, while liver metastases recurrence was not correlated with RAS status.

By Asya Ofshteyn and Allen Ho

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