Diamantis I Tsilimigras1, J Madison Hyer1, Fabio Bagante2, Alfredo Guglielmi3, Andrea Ruzzenente3, Sorin Alexandrescu4, George Poultsides5, Kazunari Sasaki6, Federico Aucejo6, Timothy M Pawlik7. 1. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH. 2. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH; Department of Surgery, University of Verona, Verona, Italy. 3. Department of Surgery, University of Verona, Verona, Italy. 4. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania. 5. Department of Surgery, Stanford University, Stanford, CA. 6. Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH. 7. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address: tim.pawlik@osumc.edu.
Abstract
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.
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.