Tsilimigras DI, Hyer JM, Bagante F, Guglielmi A, Ruzzenente A, Alexandrescu S, Poultsides G, Sasaki K, Aucejo F, Pawlik TM
BACKGROUND : Prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status following hepatic resection remains ill-defined.
METHODS : Patients undergoing hepatectomy for CRLM between 2001-2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status [wild type (wtKRAS) versus mutated (mutKRAS)] was assessed.
RESULTS : Among 1,361 patients, median number of metastatic lesions was 2 (IQR:1-3) and median size of largest metastatic lesion was 3.0cm (IQR:2.0-5.0cm) resulting in a median TBS of 4.1(IQR:2.8-6.1); KRAS status was wtKRAS (n=420, 30.9%), mutKRAS (n=251, 18.4%), and unknown (n=690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI: 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS:49.4% vs. high TBS:36.7%), as was KRAS mutational status (5-year OS, wtKRAS:48.2% vs. mutKRAS:31.1%; unknown-KRAS:44.0%)(both p<0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs. high TBS: 38.4%, p=0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs. high TBS: 26.7%, p=0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes as patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs. 37.4%, respectively; p=0.59). On multivariable analysis, while TBS was associated with OS among patients with wt-KRAS CRLM (HR 1.43, 95%CI 1.02-2.00; p=0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p=0.12).
CONCLUSION : While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.