KRAS mutations to predict survival of yttrium-90 radioembolization therapy in patients with unresectable colorectal liver metastases.

Abstract

754 Background: The significance of KRAS mutations in predicting response to Yttrium-90 radioembolization (Y90) of colorectal cancer (CRC) liver metastases is unknown. The purpose of this study was to compare overall survival (OS) in patients receiving Y90 with wild-type (wt) and mutant KRAS. Methods: Consecutive patients with unresectable CRC liver metastases and KRAS mutation status who were treated with Y90 from 2002-2014 were studied. Patient demographics, lab and molecular markers, disease stages, therapy regimens, treatment parameters, OS from primary CRC diagnosis, from liver metastasis and from first Y90 were compared between patients with KRAS wt and mutant. Kaplan-Meier estimation and Cox proportional hazard models were used for survival analysis and to assess independent prognostic factors for OS. Results: A total of 107 patients with unresectable CRC liver metastases underwent KRAS mutation analysis prior to Y90; 43 (40.2%) were mutant and 64 (59.8%) were wt. At the time of analysis, 13 patients were censored due to loss to follow-up. Groups were similar in age, sex, race, Child class, mean pre-Y90 carcino-embryonic antigen (CEA) levels, and % receiving Y90 as third-line therapy (p>0.05 for all). OS from primary diagnosis, liver metastasis, and from first Y90 was significantly greater in KRAS wt than in mutant (p=0.022, 0.002, and 0.022). Median OS from first Y90 for KRAS wt and mutant were 9.4 and 5.1 months, respectively. On multivariate analysis adjusting for age, sex, race, Child class, and pre-treatment CEA level, wt KRAS remained an independent predictor of greater survival (HR=0.64, p=0.049). Conclusions: Patients with unresectable mCRC to the liver with KRAS wt demonstrated significantly greater post-Y90 survival compared with KRAS mutant. [Table: see text]