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

Abstract

PurposeTo evaluate Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status as a prognostic factor for survival after yttrium-90 (90Y) radioembolization for colorectal cancer (CRC) liver metastases. Materials and MethodsConsecutive patients with unresectable CRC liver metastases and documented KRAS mutation status who were treated with 90Y radioembolization during the period 2007–2014 were investigated. Patient demographics, disease characteristics, therapy regimens, and overall survival (OS) from first 90Y 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. ResultsOf 186 patients, 104 underwent KRAS mutation analysis before 90Y 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 90Y 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 90Y radioembolization (66.1% vs 8.9%; P < .001). Median OS from first 90Y 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 90Y 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 90Y radioembolization. ConclusionsPatients with CRC and KRAS wt may derive greater survival benefit from 90Y radioembolization therapy than patients with KRAS mutant.