The Association of KRAS Mutation With Primary Tumor Location and Survival in Patients Undergoing Resection of Colorectal Cancers and Synchronous Liver Metastases

Niccolo Allievi; Paolo Goffredo; Alan F. Utria; Michele Pisano; Elia Poiasina; Alessandro Lucianetti; Paige Zhou; Imran Hassan


Chin Clin Oncol. 2019;8(5) 

In This Article


The SEER Program[11] provides information on cancer statistics within the U.S. It is supported by the Surveillance Research Program (SRP) within the National Cancer Institute (NCI). Data were available for a total of 18 registries representing approximately 30% of the U.S. population. The population covered by SEER is representative of the general U.S. population with regards to measures of income and education level. However, the SEER population presents a higher proportion of foreign-born patients as compared to the general U.S. population. SEER employs the International Classification of Diseases for Oncology, third edition (ICD-O-3) for histology classification.[12]

In order to select patients diagnosed with colorectal cancer and synchronous liver metastases between 2010 and 2015, the Incidence—SEER 18 Regs Custom Data Colon and Rectum Database was queried.[13] The selection of patients was conducted as follows: age older than 18 years, Stage IV colorectal adenocarcinoma with isolated liver metastases, resection of the primary tumor, nonprimary surgical procedure to distant site (i.e., patients undergoing liver resection) and known mutational status of KRAS.

Demographic variables included in the analyses were gender, age at diagnosis, year of diagnosis, ethnicity and insurance status. Clinicopathologic variables included administration of chemotherapy and radiation therapy, surgical treatment of the primary tumor and metastatic lesions, location and size of the primary tumor, involvement of the lymph nodes and KRAS status of the primary colorectal cancer. Primary tumor location was classified as 'right-sided' for lesions located from the cecum to the transverse colon and as 'left-sided' for lesions located from the splenic flexure to the rectum.

Statistical Analyses

Descriptive statistics of demographic and clinicopathologic variables were performed. Student's t-test and Chi-square test were performed to compare continuous and discrete variables, respectively. Univariate and multivariate binary logistic regression was used to recognize factors associated with m-KRAS and odds ratios (OR) and 95% CI were calculated. DSS was estimated with the Kaplan-Meier method and the log-rank test was used to evaluate statistical significance of the differences in survival. Cox proportional hazard regression was used for the multivariable survival model. Hazard ratios (HR) and 95% confidence intervals were computed for the power of association between each variable and survival.

Data analyses were performed using SEER*Stat software[14] and Statistical Package for the Social Sciences (SPSS) software (version 20.0; SPSS Inc., Chicago, IL, USA). P values were considered significant if <0.05 and all tests were two-sided. Considering that data included in the SEER Database is publicly available and de-identified, approval by an institutional review board was not considered necessary for the current study.