KRAS Status as an Independent Prognostic Factor for Survival after Yttrium-90 Radioembolization Therapy for Unresectable Colorectal Cancer Liver Metastases

Purpose: To evaluate Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status as a prognostic factor for survival after yttrium-90 (Y-90) radioembolization for colorectal cancer (CRC) liver metastases. Materials and Methods: Consecutive patients with unresectable CRC liver metastases and documented KRAS mutation status who were treated with Y-90 radioembolization during the period 2007-2014 were investigated. Patient demographics, disease characteristics, therapy regimens, and overall survival (OS) from first Y-90 radioembolization were compared between patients with KRAS wild-type (wt) and mutant status. Kaplan-Meier estimation and Cox regression were used for survival analysis and to assess independent prognostic factors for OS. Results: Of 186 patients, 104 underwent KRAS mutation analysis before Y-90 radioembolization, with 45 (43.3%) identified as mutant. The wt and mutant groups were similar in demographics, liver status, overall performance status, and tumor characteristics (all P > .05). Mean time from liver metastasis to Y-90 radioembolization was greater in patients with KRAS wt status (P = .033). A greater percentage of wt patients received anti-epidermal growth factor receptor therapies before Y-90 radioembolization (66.1% vs 8.9%; P < .001). Median OS from first Y-90 radioembolization was significantly greater in KRAS wt patients (9.5 mo vs 4.8 mo; P = .041). Univariate analysis identified Child-Pugh class, carcinoembryonic antigen (CEA), chemotherapy after Y-90 radioembolization, KRAS status, and treatment-induced toxicity as prognostic factors for OS. Multivariate Cox regression analysis demonstrated Child-Pugh class, CEA, and KRAS status to be independent prognostic factors for OS, even when correcting for the effect of chemotherapy after Y-90 radioembolization. Conclusions: Patients with CRC and KRAS wt may derive greater survival benefit from Y-90 radioembolization therapy than patients with KRAS mutant.