Connecting cancer biology and clinical outcomes to imaging in KRAS mutant and wild-type colorectal cancer liver tumors following selective internal radiation therapy with yttrium-90.

Abstract

To determine whether pathologic colorectal tumor KRAS mutation status is correlated with progression-free survival (PFS) by imaging after selective internal radiation therapy with Yttrium-90 (SIRT Y90) for metastatic colorectal cancer in the liver (mCRC). This was an IRB approved, HIPAA compliant retrospective cohort study. Consecutive patients with unresectable mCRC with documented KRAS mutation status treated at a single center from 2002 to 2013 with SIRT Y90 were investigated. Treatment response was compared between KRAS wild-type (wt) and mutant (mut) using an anatomic tumor response criteria based on RECIST 1.0. Kaplan-Meier estimation and Cox regression analysis were used to measure progression-free survival (PFS) and to assess independent prognostic factors for PFS. 82 of 186 patients met review criteria. 33 (40.2%) patients were identified as KRAS mut. PFS was longer in KRAS wt (median 166days [95% CI 96-258days]) vs. mut (median 91days [95% CI 79-104days], p=0.002). KRAS mut patients were 1.48 times more likely to progress at first follow-up imaging than wt (95% CI 1.06-2.08, p=0.024). Univariate analysis identified high pre-SIRT Y90 INR, KRAS wt, any use of anti-EGFR therapy, and post-SIRT Y90 chemotherapy as prognostic factors for longer PFS. In multivariate analysis, only KRAS wt was an independent prognostic factor for longer PFS (RR: 1.80 [95% CI 1.08-2.99], p=0.024). Longer PFS is associated with KRAS wt vs. mut following SIRT Y90.