Primary Tumor Localization is Associated with Progression-free Survival and Overall Survival after Selective-Internal-Radio-Therapy of Liver Metastases in Metastatic Colorectal Cancer

Abstract This retrospective study aimed to investigate whether the differing biology of right-sided primary tumors (RSP) and left-sided primary tumors (LSP) in metastatic colorectal cancer (mCRC) affects survival outcomes following selective internal radiation therapy (SIRT). A cohort of 140 mCRC patients with liver metastases treated with SIRT between 2009 and 2016 was analyzed. Patients were stratified by tumor localization (RSP: proximal colon; LSP: distal colon and rectum), clinical, histopathological, and molecular data, were collected. Survival outcomes (OS and PFS) were evaluated using Kaplan-Meier analysis. Cox regression analysis identified independent predictors of survival, and subgroup analyses examined differences between RSP and LSP patients. Of the patients, 80.7% had LSP, and 19.3% had RSP. RSP patients demonstrated more aggressive tumor biology, with a higher frequency of poorly differentiated tumors (G3), extrahepatic metastases and K-RAS mutations. Median OS was significantly longer for LSP patients (7.0 months) compared to RSP patients (4.0 months, p<0.005). Similarly, PFS was longer for LSP patients (3.0 months) than for RSP patients (1.6 months, p<0.032). Multivariable Cox regression analysis revealed that K-RAS mutation (HR 3.345, p=0.017), N2 lymph node involvement (HR 2.458, p=0.015), and RSP localization (HR 0.338, p=0.001) were independently associated with poor survival. This study demonstrates that right-sided tumor localization, K-RAS mutation, and N2 lymph node involvement are key predictors of poor survival following SIRT in mCRC patients. RSP tumors, with distinct molecular and clinical profiles, exhibit shorter median OS and PFS after SIRT compared to LSP tumors.